Biochemistry of the tale transcription factors PREP, MEIS, and PBX in vertebrates.

TALE (three amino acids loop extension) homeodomain transcription factors are required in various steps of embryo development, in many adult physiological functions, and are involved in important pathologies. This review focuses on the PREP, MEIS, and PBX sub-families of TALE factors and aims at giving information on their biochemical properties, i.e., structure, interactors, and interaction surfaces. Members of the three sets of protein form dimers in which the common partner is PBX but they can also directly interact with other proteins forming higher-order complexes, in particular HOX. Finally, recent advances in determining the genome-wide DNA-binding sites of PREP1, MEIS1, and PBX1, and their partial correspondence with the binding sites of some HOX proteins, are reviewed. These studies have generated a few general rules that can be applied to all members of the three gene families. PREP and MEIS recognize slightly different consensus sequences: PREP prefers to bind to promoters and to have PBX as a DNA-binding partner; MEIS prefers HOX as partner, and both PREP and MEIS drive PBX to their own binding sites. This outlines the clear individuality of the PREP and MEIS proteins, the former mostly devoted to basic cellular functions, the latter more to developmental functions.

Prep1 (pKnox1)-deficiency leads to spontaneous tumor development in mice and accelerates EmuMyc lymphomagenesis: a tumor suppressor role for Prep1.

The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1(i/i) embryos, expressing the gene at 2% of the normal levels, survive pregnancy and live a normal-length life. Later in life, however, these mice develop spontaneous pre-tumoral lesions or solid tumors (lymphomas and carcinomas). In addition, transplantation of E14.5 fetal liver (FL) Prep1(i/i) cells into lethally irradiated mice induces lymphomas. In agreement with the above data, haploinsufficiency of a different Prep1-deficient (null) allele accelerates EmuMyc lymphoma growth. Therefore Prep1 has a tumor suppressor function in mice. Immunohistochemistry on tissue micrroarrays (TMA) generated from three distinct human cohorts comprising a total of some 1000 human tumors revealed that 70% of the tumors express no or extremely low levels of Prep1, unlike normal tissues. Our data in mice are thus potentially relevant to human cancer.

Characterization of two new alleles at the goat CSN1S2 locus.

Two novel alleles at the goat CSN1S2 locus have been identified: CSN1S2(F) and CSN1S2(D). Sequence analyses revealed that the CSN1S2(F) allele is characterized by a G --> A transition at the 13th nucleotide in exon 3 changing the seventh amino acid of the mature protein from Val to Ile. The CSN1S2(D) allele, apparently associated with a decreased synthesis of alpha s2-casein, is characterized by a 106-bp deletion, involving the last 11 bp of the exon 11 and the first 95 bp of the following intron. Methods (PCR-RFLP and PCR) for identification of carriers of these alleles have been developed.

An allele associated with a non-detectable amount of alpha s2 casein in goat milk.

The goat CSN1S2 locus is characterized by the presence of three alleles, A, B and C, all associated with about 2.5 g/l of protein per allele. The SDS-PAGE analysis of 441 individual milk samples obtained from goats belonging to a population reared in Southern Italy showed that the milk produced by three goats did not apparently contain alpha s2-casein, whereas milk produced by 37 goats showed a less intense electrophoretic band of this casein fraction (about 50%). These results can be explained by hypothesizing the presence of another allele at this locus, CSN1S2o, associated with a 'null' content of alpha s2-casein. Southern blot, PCR and PCR-RFLP analyses of the DNA region containing the CSN1S2 gene of individuals producing milk with and without alpha s2-casein did not show differences between the two groups. As a consequence, goats producing milk without alpha s2-casein carry an apparently intact gene. The first results obtained by sequencing part of the CSN1S2o allele revealed a G-->A transition at nucleotide 80 of the 11th exon which creates a stop codon and could be responsible for the absence of the alpha s2-casein in goat milk. This mutation eliminates a NcoI restriction site. A test based on this polymorphism has been established in order to identify carriers of the CSN1S2o allele.

Noun versus verb emphasis in Italian mother-to-child speech.

This paper examines naturalistic adult-to-child speech produced by 15 Italian middle-class mothers to determine which specific patterns characterize linguistic input to children at 1;4 and 1;8. Since Italian is a pro-drop language, we expect that adult-to-child speech will show a bias towards a more salient semantic and morphological significance of verbs relative to nouns. We expect that verbs will more likely occupy the sentence-initial position, and have more morphological inflections relative to nouns. Mother-to-child speech was coded for type and token frequency, utterance position, and morphological variation of nouns and verbs. The results confirm our predictions. Namely, Italian-speaking mothers produced verb types and tokens more frequently than noun types and tokens, they placed verbs more frequently than nouns in salient utterance position, and they morphologically marked verb stems more than noun stems.

Visuo-spatial and linguistic abilities in a twin with Williams syndrome.

The present study reports a case of dizygotic twins, one boy with Williams syndrome (WS) and one typically developing girl, and compares their neuropsychological profiles. The goal of the present authors was to verify whether the child with WS displayed a cognitive profile which is unique to the syndrome. Several tests designed to assess visuo-perceptual, visuo-motor, linguistic and memory abilities were administered to both children when they were 10.9 years old. Compared to his sister, the boy with WS displayed a homogeneous developmental delay in both non-verbal and verbal abilities. He achieved a level of performance similar to his sister only in facial recognition, phonological word fluency and memory for phonologically similar words. Furthermore, despite the overall delayed performance of the boy, both the twins displayed a cognitive profile characterized by strength in lexical comprehension and relative weakness in visuo-motor abilities.

Gestures and words in early development of children with Down syndrome.

This study investigated the development of language and communication in children with Down syndrome (DS). More specifically, the aim was to examine the relations among verbal comprehension, verbal production, and gesture production in the very early stages of development. Forty children (age range: 10-49 months) with DS and 40 children with normal development (age range: 8-17 months) participated in this study. Children with DS came from two Italian health centers. The communicative and linguistic development of children with DS was measured by administering the Italian version of the MacArthur Communicative Development Inventory. The children with DS were severely delayed when compared with normally developing children in reaching the developmental stages. In such children a dissociation emerged between verbal comprehension and production, in favor of comprehension, whereas a synchronous development was found between vocal lexical comprehension and gestural production. The individual differences previously reported in these children are also evident in all domains examined. There were no significant differences between children with DS and typically developing controls matched for lexical comprehension on verbal production. However the two groups differed significantly in gestural development, suggesting a "gesture advantage" in children with DS compared with controls matched for word comprehension. Some possible reasons for this dissociative profile are discussed.