Congenital factor XIII deficiency in Switzerland: from the worldwide first case in 1960 to its molecular characterisation in 2005.

Coagulation factor XIII (FXIII) has a major role in the final stage of blood coagulation, is important for wound healing and maintaining pregnancy. Severe congenital FXIII deficiency is a rare disorder with 1 patient in 1-3 million. Untreated, it causes bleeding events, with intracranial haemorrhage being the major cause of death, impaired wound healing, and abortion. FXIII deficiency was traditionally diagnosed using the clot solubility test, but quantitative FXIII activity and antigen assays are preferred today. Treatment consists of replacement therapy with FXIII concentrates administered every 4-6 weeks. The molecular-genetic causes of FXIII deficiency are mutations in the genes coding for the FXIII A- and B-subunits. More than 60 mutations distributed throughout the FXIII A-subunit gene have been identified so far and 4 mutations in the FXIII B-subunit gene. The first case of congenital FXIII deficiency was reported in Switzerland in 1960. In Switzerland we observed a disproportionately high incidence, which can be explained in part by a founder effect. In this article, we summarise general facts on severe congenital FXIII deficiency, and we characterise all FXIII deficient patients living in Switzerland, including the first case described in 1960 who is a member of a large family originating from the canton of Uri.

Drosophila peripodial cells, more than meets the eye?

Drosophila imaginal discs (appendage primordia) have proved invaluable for deciphering cellular and molecular mechanisms of animal development. By combining the accessibility of the discs with the genetic tractability of the fruit fly, researchers have discovered key mechanisms of growth control, pattern formation and long-range signaling. One of the principal experimental attractions of discs is their anatomical simplicity - they have long been considered to be cellular monolayers. During larval stages, however, the growing discs are 2-sided sacs composed of a columnar epithelium on one side and a squamous 'peripodial' epithelium on the other. Recent studies suggest important roles for peripodial epithelia in processes previously assumed to be confined to columnar cell monolayers.

[Travel with small children]. / Reisen mit Kleinkindern.

Travelling with young children can lead to difficult situations. Accordingly, travel preparations should be geared towards the needs of the youngest with appropriate medical advise. Young children tolerate most means of transportation. When travelling long distances by car, clear rules ought to be established, and many children require antiemetic measures. With regards to traffic safety, compromises during family vacation are not acceptable. Travelling by plane or train is less stressful than travelling by bus or car. As a medical advisor, one ought to be familiar with age limits for certain immunizations and medications (particularly antimalarial agents). Parental knowledge of modern rules for oral rehydration in cases of traveller's diarrhoea is frequently insufficient. Whenever possible, travelling with young children to high risk regions should be avoided.

Provision of supplementary fluids to breast fed infants and later breast feeding success.

It has been shown that altering hospital policies in a way to avoid interference of routine prescriptions with initiation of breast feeding and to provide active encouragement to mothers and personnel can result in significant benefit for later breast feeding success. It is less clear, however, which of the elements of a promotional programme such as UNICEF/WHO's "ten steps to successful breast feeding" are absolutely essential and which can be adapted to local cultural habits. We performed an open randomized multicenter study in Switzerland to evaluate, whether restriction of supplementary fluids for breast fed infants in the first week of life and strict avoidance of artificial teats and pacifiers affects later breast feeding success. Follow up to 6 months was ensured by mailed questionnaires. 602 mother infant pairs were enrolled. Of 294 infants in the intervention group 39% were excluded from the final analysis because of protocol violations, mainly maternal request for the use of pacifiers or bottles. Though the number of dextrin maltose supplements during the first two days (1.7 vs. 2.2 on day 1, 2.2 vs. 2.6 on day 2) and the percentage of infants receiving any supplement (85% vs. 96.6%) was significantly smaller in the intervention group, the difference was disappointingly small. The prevalence of breast feeding was 100% vs. 99% at day 5, 88% vs. 88% at 2 months, 75% vs. 71% at 4 months and 57% vs. 55% at 6 months, none of the differences being significant. We conclude that rigorous adherence to all of the ten steps may encounter obstinate resistance from cultural habits even in a population highly favourable to breast feeding. An improvement in adherence does not necessarily lead to better breast feeding success. The results of the few comparable studies in the literature show also that cultural practices during the first months of life may influence profoundly the long term effects of interventions during the first days of life.

Stem cell plasticity in mammals and transdetermination in Drosophila: common themes?

Stem cells have been identified in a number of mammalian tissues (e.g. bone marrow, muscle, gut, skin, and neural tissues). Until recently, it was generally believed that the differentiation potential of a mammalian somatic stem cell is restricted to one tissue only, as in the case of hematopoietic stem cells differentiating into hematopoietic cells. In this sense, somatic stem cells are limited in their differentiation potential. Several lines of evidence now challenge the idea of unilateral development. New reports show mammalian somatic stem cells can, in the course of regeneration, repopulate heterologous cell systems and therefore possess a surprisingly broad spectrum of differentiation potential. Thus, mammalian stem cells are apparently capable of fate changes between stem cell systems, although the mechanisms leading to such changes are unclear. Mechanistic models for fate changes have been proposed in Drosophila, specifically for transdetermination of imaginal discs. Imaginal discs of the larva are the primordia of the adult exoskeleton and appendages, for example, legs, and antennae. Transplantation experiments of imaginal discs have shown that discs are determined for their disc identity. Transdetermination in Drosophila refers to cases when, after regenerative cell divisions, imaginal disc cells change from one state of determination to another, initiating a pathway of differentiation leading to structures other than those corresponding to the initial state or determination; for example, an antennal imaginal disc transdetermines to a leg imaginal disc. A fate change is thus possible in both mammalian somatic stem cells and Drosophila imaginal discs following transplantation and subsequent proliferation. Here we summarize and compare observations made in such cases of stem cell and imaginal disc differentiation.

Peripodial cells regulate proliferation and patterning of Drosophila imaginal discs.

Cells employ a diverse array of signaling mechanisms to establish spatial patterns during development. Nowhere is this better understood than in Drosophila, where the limbs and eyes arise from discrete epithelial sacs called imaginal discs. Molecular-genetic analyses of pattern formation have generally treated discs as single epithelial sheets. Anatomically, however, discs comprise a columnar cell monolayer covered by a squamous epithelium known as the peripodial membrane. Here we demonstrate that during development, peripodial cells signal to disc columnar cells via microtubule-based apical extensions. Ablation and targeted gene misexpression experiments demonstrate that peripodial cell signaling contributes to growth control and pattern formation in the eye and wing primordia. These findings challenge the traditional view of discs as monolayers and provide foundational evidence for peripodial cell function in Drosophila appendage development.

Cyclin A and B functions in the early Drosophila embryo.

In eukaryotes, mitotic cyclins localize differently in the cell and regulate different aspects of the cell cycle. We investigated the relationship between subcellular localization of cyclins A and B and their functions in syncytial preblastoderm Drosophila embryos. During early embryonic cycles, cyclin A was always concentrated in the nucleus and present at a low level in the cytoplasm. Cyclin B was predominantly cytoplasmic, and localized within nuclei only during late prophase. Also, cyclin B colocalized with metaphase but not anaphase spindle microtubules. We changed maternal gene doses of cyclins A and B to test their functions in preblastoderm embryos. We observed that increasing doses of cyclin B increased cyclin B-Cdk1 activity, which correlated with shorter microtubules and slower microtubule-dependent nuclear movements. This provides in vivo evidence that cyclin B-Cdk1 regulates microtubule dynamics. In addition, the overall duration of the early nuclear cycles was affected by cyclin A but not cyclin B levels. Taken together, our observations support the hypothesis that cyclin B regulates cytoskeletal changes while cyclin A regulates the nuclear cycles. Varying the relative levels of cyclins A and B uncoupled the cytoskeletal and nuclear events, so we speculate that a balance of cyclins is necessary for proper coordination during these embryonic cycles.

[Development of formerly preterm infants with a birth weight of below 1500 grams: concept and results of a follow-up program in up to school-aged children in central Switzerland]. / Entwicklung ehemaliger Frühgeborener mit einem Geburtsgewicht unter 1500 Gramm: Konzept und Resultate von Nachkontrollen bis zum Schulalter in der Zentralschweiz.

AIM: To document the psychomotor development and general health of former very low birthweight infants born between 1980 and 1986 from birth up to school age. We wished to evaluate the quality of neonatal intensive care in Central Switzerland over this time period and test the reliability of a patient-oriented follow-up programme. If successful, the latter could perhaps serve as a model for a national follow-up programme in Switzerland. METHODS: Information regarding three different developmental periods was collected. The medical records of the perinatal period were used to abstract details of labour and delivery and the neonatal period. The records of the infant follow-up programme were used to describe psychomotor development between 0 and 24 months of age. The current health status and school performance were evaluated using a questionnaire sent to parents and teachers. RESULTS: Of 139 infants born with a birthweight of < or = 1500 g, 102 were discharged home (mortality rate 26.6%). One third was not screened for hearing deficits or retinopathy of prematurity. Eighty-two were seen in the infant follow-up programme between 0 and 24 months of age. Seventy-seven percent of these infants were judged to be normal and discharged from the infant follow-up programme; 1/5 of these infants had had transient motor problems treated by physical therapy. Twenty-three percent of the infants seen in infant follow-up had persistent but mainly minor motor handicaps, and only two infants (2%) had multiple handicaps. At school age, data from 99 of the 102 surviving infants was collected. Ninety-six percent attended regular school, but almost half of them had significant school problems and required professional help. These problems correlated poorly with the results of examinations during early childhood (positive predictive value 67%). CONCLUSIONS: These long-term results of a population of preterm infants born in Central Switzerland in the 1980s are encouraging. To ensure completeness of early ophthalmological and audiological examinations of all former small preterm infants, neonatal follow-up programmes should adhere to uniform guidelines.

Oral vitamin K1 prophylaxis for newborns with a new mixed-micellar preparation of phylloquinone: 3 years experience in Switzerland.

UNLABELLED: In 1995, a new water-soluble mixed-micellar analogue of vitamin K1 (Konakion MM paediatric) was introduced in Switzerland to replace the formerly used fat-soluble Konakion drops for the prevention of vitamin K1-deficiency-bleeding (VKDB) in infants. According to the new guidelines, an oral dose of 2 mg is given after birth and again on the 4th day of life. We examined the compliance with these guidelines and the impact on the incidence of VKDB. To assess compliance, questionnaires were sent to all hospitals with delivery services 6 months after the introduction of the new guidelines. Using the database of the Swiss Paediatric Surveillance Unit (SPSU) which records rare paediatric diseases, we assessed the incidence of VKDB in Switzerland between July 1995 and June 1998. In addition, we determined the precise circumstances under which the episodes of VKDB occurred. More than 99% of infants received vitamin K1 prophylaxis. Since July 1995, 93% of newborns have received prophylaxis according to the new guidelines; the remaining infants were given fat-soluble Konakion drops or parenteral vitamin K1. Within 3 years, one case of classical and 12 cases of late-onset VKDB (11 confirmed, 1 probable) were reported to the SPSU. Of the 11 confirmed late-onset cases, 7 received the recommended prophylaxis, whereas 3 had not and 1 had been given fat-soluble Konakion drops. All confirmed cases of late-onset VKDB occurred in fully breast-fed infants and 8 of 11 had hepatobiliary disease. CONCLUSION: With the introduction of two oral doses of a mixed-micellar vitamin K1 preparation administered in the 1st week of life, the incidence of late vitamin K1-deficiency-bleeding has decreased from 7.2:100,000 between 1986-1987 to 2.8:100,000 between 1995 and 1998. This regimen may be suitable for prophylaxis of vitamin K1-deficiency-bleeding, however, it does not fully protect infants with cholestatic disease from late-onset bleeding. If oral prophylaxis is considered for these infants, vitamin K1 has to be administered repeatedly to all infants during the breast feeding period.

Hedgehog is required for activation of engrailed during regeneration of fragmented Drosophila imaginal discs.

Surgically fragmented Drosophila appendage primordia (imaginal discs) engage in wound healing and pattern regulation during short periods of in vivo culture. Prothoracic leg disc fragments possess exceptional regulative capacity, highlighted by the ability of anterior cells to convert to posterior identity and establish a novel posterior compartment. This anterior/posterior conversion violates developmental lineage restrictions essential for normal growth and patterning of the disc, and thus provides an ideal model for understanding how cells change fate during epimorphic pattern regulation. Here we present evidence that the secreted signal encoded by hedgehog directs anterior/posterior conversion by activating the posterior-specific transcription factor engrailed in regulating anterior cells. In the absence of hedgehog activity, prothoracic leg disc fragments fail to undergo anterior/posterior conversion, but can still regenerate missing anterior pattern elements. We suggest that hedgehog-independent regeneration within the anterior compartment (termed integration) is mediated by the positional cues encoded by wingless and decapentaplegic. Taken together, our results provide a novel mechanistic interpretation of imaginal disc pattern regulation and permit speculation that similar mechanisms could govern appendage regeneration in other organisms.

Cell determination and transdetermination in Drosophila imaginal discs.

Drosophila imaginal discs, the precursors of the adult fly appendages, are an important system for studying mechanisms of cell determination. How the different imaginal discs acquire and maintain their appendage-specific determined states are problems that have been addressed using experimental embryology as well as genetic and molecular approaches. Here we discuss the concept of cell determination and describe what is known about how determination is established and maintained in imaginal disc cells. The phenomenon of imaginal disc transdetermination, originally discovered in the 1960s, has remained an intriguing problem for understanding imaginal disc cell determination. We review the topic of imaginal disc transdetermination and describe how recent results from molecular genetic approaches have provided new insights into imaginal disc transdetermination and determination. We also discuss how an understanding of imaginal disc transdetermination can aid our understanding of parallel phenomena in other organisms, including human metaplasias.

[Routine preventive vaccinations]. / Routinemässige Schutzimpfungen.

In 1996, a second measles, mumps and rubella (MMR) vaccination at the time of school entry was included in the Swiss Childhood Immunization schedule, and universal hepatitis B immunization will likely be added in 1998. An additional innovation is the possibility to use acellular pertussis vaccines which have a lower rate of side effects. Each physician who is involved in immunizations should be familiar with the arguments that support the official immunization recommendations in order to be able to provide competent advice to patients or their parents.

A molecular basis for transdetermination in Drosophila imaginal discs: interactions between wingless and decapentaplegic signaling.

We are investigating how Drosophila imaginal disc cells establish and maintain their appendage-specific determined states. We have previously shown that ectopic expression of wingless (wg) induces leg disc cells to activate expression of the wing marker Vestigial (Vg) and transdetermine to wing cells. Here we show that ectopic wg expression non-cell-autonomously induces Vg expression in leg discs and that activated Armadillo, a cytosolic transducer of the Wg signal, cell-autonomously induces Vg expression in leg discs, indicating that this Vg expression is directly activated by Wg signaling. We find that ubiquitous expression of wg in leg discs can induce only dorsal leg disc cells to express Vg and transdetermine to wing. Dorsal leg disc cells normally express high levels of decapentaplegic (dpp) and its downstream target, optomotor-blind (omb). We find that high levels of dpp expression, which are both necessary and sufficient for dorsal leg development, are required for wg-induced transdetermination. We show that dorsalization of ventral leg disc cells, through targeted expression of either dpp or omb, is sufficient to allow wg to induce Vg expression and wing fate. Thus, dpp and omb promote both dorsal leg cell fate as well as transdetermination-competent leg disc cells. Taken together, our results show that the Wg and Dpp signaling pathways cooperate to induce Vg expression and leg-towing transdetermination. We also show that a specific vg regulatory element, the vg boundary enhancer, is required for transdetermination. We propose that an interaction between Wg and Dpp signaling can explain why leg disc cells transdetermine to wing and that our results have implications for normal leg and wing development.

UNICEF/WHO baby-friendly hospital initiative: does the use of bottles and pacifiers in the neonatal nursery prevent successful breastfeeding? Neonatal Study Group.

UNLABELLED: To promote breastfeeding, UNICEF/WHO have launched the "baby-friendly hospital initiative" focusing on hospital care routines during delivery and the first days of life. In industrialised countries, two aspects of the initiative have raised controversy: how do restriction of supplemental feedings and ban of bottles and pacifiers affect long-term breastfeeding performance? From ten centres 602 healthy newborns were randomly assigned either to a UNICEF group with restrictive fluid supplements and avoidance of bottles and pacifiers during the first 5 days of life, or to a standard group with conventional feeding practice. Breastfeeding was encouraged in both groups. The main study endpoints were the prevalences of breast-feeding on day 5, and after 2, 4 and 6 months. Of the newborns 46% violated the UNICEF protocol, mostly because of maternal requests to give a pacifier or supplements by bottle. In the standard group, the drop-out rate was 9.7%. No significant differences in breastfeeding frequency and duration could be found: (UNICEF vs standard) day 5: 100% vs 99%; 2 months: 88% vs 88%; 4 months: 75% vs 71%; 6 months: 57% vs 55%. Inclusion of drop-outs due to pacifier use did not alter the results. CONCLUSION: In our study population fluid supplements offered by bottle with or without the use of pacifiers during the first 5 days of life were not associated with a lower frequency or shorter duration of breastfeeding during the first 6 months of life.

Plasma vitamin K1 and PIVKA-II after oral administration of mixed-micellar or cremophor EL-solubilized preparations of vitamin K1 to normal breast-fed newborns.

BACKGROUND: Vitamin K1 prophylaxis in neonates is required for prevention of vitamin K1 deficiency bleeding. Although intramuscular administration of vitamin K1 is safe, this invasive method is not generally accepted. We therefore examined the pharmacokinetics of two orally administered vitamin K1 preparations in normal, fully breast-fed newborns. METHODS: Within 1 hour of birth, each baby was randomized to a 2 mg dose of either a conventional Cremophor EL-solubilized preparation of vitamin K1 (Konakion drops, F. Hoffmann-La Roche, n = 16), or a new mixed-micellar preparation of vitamin K1 (Konakion MM, F. Hoffmann-La Roche, n = 14). The concentrations of vitamin K1, des-gamma-carboxyprothrombin (PIVKA-II), and total bound bilirubin were measured in plasma samples taken at 24 hours, 4 days, and 24 days after birth. RESULTS: The median concentration of plasma vitamin K1 was higher at all three time points in the group that received the mixed-micellar preparation, but the difference was only significant (p < 0.05) at 4 days. At 24 hours and 4 days, PIVKA-II was detectable in a significantly lower proportions of infants receiving the new mixed-micellar preparation than those receiving the Cremophor EL preparation (21% vs. 75% at 24 hours, p < 0.05 and 14% vs. 50% at 4 days, p < 0.05). None of the infants in the study had detectable PIVKA-II levels 24 days after birth. CONCLUSIONS: Our results suggest that when given orally, the mixed-micellar preparation is superior to the conventional formulation because it increases plasma vitamin K1 concentrations to higher levels, suggesting superior bioavailability, and decreases PIVKA-II concentrations more efficiently, suggesting a faster pharmacodynamic response.

Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K.

UNLABELLED: There is consensus that late vitamin K deficiency bleeding (VKDB) should be prevented by vitamin K prophylaxis. One single dose of 1 mg vitamin K1 is effective if given i.m. or s.c., but not if given orally. Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established. Different oral dose schedules are presently used in different countries. In Australia, Germany, The Netherlands and Switzerland active surveillance data on late VKDB were collected in a similar manner and failure rates compared. Identical case definitions were used. There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries: (1) daily supplementation of low dose vitamin K (25 micrograms) for breast-fed infants (The Netherlands); (2) 3 x 1 mg orally [Australia (January 1993-March 1994) and Germany (December 1992-December 1994)]; (3) 1 mg vitamin K i.m. (Australia since March 1994); and (4) 2 x 2 mg vitamin K (new mixed micellar preparation) (Switzerland). The respective failure rates per 100,000 live births (including cases given all recommended doses and those given incomplete prophylaxis) were for strategy: (1) 0.2 (0-1.3) in The Netherlands; (2) 2.3 (95% CI 1.6-3.4) in Germany and 2.5 (1.1-4.8) in Australia (oral prophylaxis); (3) Australia (i.m. prophylaxis) 0 (0-0.9); and (4) 3.6 (0.7-10.6) in Switzerland. The failure rates for complete prophylaxis only were: strategy (1) 0 (0-0.7) in The Netherlands; (2) 1.8 (1.1-2.8) in Germany and 1.5 (0.5-3.6) in Australia; (3) Australia (i.m.) 0 (0-0.9); and (4) 1.2 (0-6.5) in Switzerland. CONCLUSIONS: The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m. vitamin K prophylaxis. A daily low oral dose of 25 micrograms vitamin K1 following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis. The effectiveness of the "mixed-micellar" preparation of vitamin K1 needs further study.

A vertical (pseudodominant) pattern of inheritance in the autosomal recessive disease primary hyperoxaluria type 1: lack of relationship between genotype, enzymic phenotype, and disease severity.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of alanine:glyoxylate aminotransferase (encoded by the AGXT gene). Primary hyperoxaluria type 1 is characterized by the elevated urinary excretion of oxalate and glycolate, and the deposition of insoluble calcium oxalate in the renal parenchyma and urinary tract. In the present study, we investigated an unusual family containing four affected individuals in two different generations. Based on our genetic, enzymic, metabolic, and clinical analyses, we have come to the following conclusions. First, although the pattern of inheritance of PH1 is usually horizontal (ie, all patients in the same generation), as expected for an autosomal recessive disease, it can sometimes show a vertical (pseudodominant) pattern of inheritance (ie, patients in more than one generation) due to the segregation within a family of three, rather than two, mutant AGXT alleles. Second, affected members of such a family can manifest very different clinical phenotypes both within and between generations. Although the clinical differences between generations might be at least partly due to differences in AGXT genotype, differences can equally occur within the same generation in individuals who possess the same AGXT genotype. Finally, individuals with PH1 at the level of the AGXT genotype might remain asymptomatic and undiagnosed for many years. The consequences of these findings for the clinical management and genetic counseling of families with PH1 are profound and wide-ranging.

Ectopic expression of wingless in imaginal discs interferes with decapentaplegic expression and alters cell determination.

We have expressed the segment polarity gene wingless (wg) ectopically in imaginal discs to examine its regulation of both ventral patterning and transdetermination. By experimentally manipulating the amount of Wg protein, we show that different thresholds of Wg activity elicit different outcomes, which are mediated by regulation of decapentaplegic (dpp) expression and result in alterations in the expression of homeotic genes. A high level of Wg activity leads to loss of all dorsal pattern elements and the formation of a complete complement of ventral pattern elements on the dorsal side of legs, and is correlated with repression of dpp expression. wg expression in dorsal cells of each disc also leads to dose-dependent transdetermination in those cells in homologous discs such as the labial, antennal and leg, but not in cells of dorsally located discs. When dpp expression is repressed by high levels of Wg, transdetermination does not occur, confirming that dpp participates with wg to induce transdetermination. These and other experiments suggest that dorsal expression of wg alters disc patterning and disc cell determination by modulating the expression of dpp. The dose-dependent effects of wg on dpp expression, ventralization of dorsal cells and transdetermination support a model in which wg functions as a morphogen in imaginal discs.

Activation of transcription in Drosophila embryos is a gradual process mediated by the nucleocytoplasmic ratio.

We have observed that zygotic transcription does not initiate at a single point in Drosophila embryos. Rather, a gene initiates transcription in a few nuclei of a fraction of embryos. During succeeding cycles, the frequency of transcribing embryos, and of nuclei transcribing in those embryos, gradually increases. For the fushi tarazu (ftz) gene, the timing of this process is regulated by the concentration of the maternally loaded, repressing transcription factor tramtrack (ttk). Altering the dose of Ttk protein in embryos shifts the activation of ftz transcription either forward or backward during development but does not effect Krüppel (Kr) activation. We have observed that the transcription of several genes, including ftz, is triggered in embryos at a critical nuclear density; therefore, we suggest that titration of transcription factors like ttk by the nucleocytoplasmic ratio triggers zygotic transcription in Drosophila.

Autonomous and nonautonomous Notch functions for embryonic muscle and epidermis development in Drosophila.

The Notch (N) gene encodes a cell signaling protein that mediates neuronal and epidermal determination in Drosophila embryos. N also regulates several aspects of myogenic development; embryos lacking N function have too many muscle founder cells and fail to properly differentiate somatic muscle. To identify cell-autonomous requirements for Notch function during muscle development, we expressed a Notch minigene in the mesoderm, but not in the ectoderm, of amorphic N-embryos. In these embryos, muscle founder hypertrophy is rescued, indicating that Notch is autonomously required by mesoderm cells to regulate the proper number of muscle founders. However, somatic muscle differentiation is only partially normalized, suggesting that Notch is also required in the ectoderm for proper muscle development. Additionally, mesodermal expression of Notch partially rescues epidermal development in overlying neurogenic ectoderm. This is unexpected, since previous studies suggest that Notch is autonomously required by proneural ectoderm cells for epidermal development. Mesodermal expression of a truncated Notch protein lacking the extracellular domain does not rescue ventral epidermis, suggesting that the extra-cellular domain of Notch can non-autonomously rescue epidermal development across germ layers.