A precise balance of TETRASPANIN1/TORNADO2 activity is required for vascular proliferation and ground tissue patterning in Arabidopsis.

The molecular mechanisms guiding oriented cell divisions in the root vascular tissues of Arabidopsis thaliana are still poorly characterised. By overlapping bulk and single-cell transcriptomic datasets, we unveiled TETRASPANIN1 (TET1) as a putative regulator in this process. TET1 is expressed in root vascular cells, and loss-of-function mutants contain fewer vascular cell files. We further generated and characterised a CRISPR deletion mutant and showed, unlike previously described mutants, that the full knock out is additionally missing endodermal cells in a stochastic way. Finally, we show that HA-tagged versions of TET1 are functional in contrast to fluorescent TET1 translational fusions. Immunostaining using HA-TET1 lines complementing the mutant phenotype suggested a dual plasma membrane and intracellular localisation in the root vasculature and a polar membrane localisation in the young cortex, endodermal and initial cells. Taken together, we show that TET1 is involved in both vascular proliferation and ground tissue patterning. Our initial results pave the way for future work to decipher its precise mode of action.

Conditional destabilization of the TPLATE complex impairs endocytic internalization.

In plants, endocytosis is essential for many developmental and physiological processes, including regulation of growth and development, hormone perception, nutrient uptake, and defense against pathogens. Our toolbox to modulate this process is, however, rather limited. Here, we report a conditional tool to impair endocytosis. We generated a partially functional TPLATE allele by substituting the most conserved domain of the TPLATE subunit of the endocytic TPLATE complex (TPC). This substitution destabilizes TPC and dampens the efficiency of endocytosis. Short-term heat treatment increases TPC destabilization and reversibly delocalizes TPLATE from the plasma membrane to aggregates in the cytoplasm. This blocks FM uptake and causes accumulation of various known endocytic cargoes at the plasma membrane. Short-term heat treatment therefore transforms the partially functional TPLATE allele into an effective conditional tool to impair endocytosis. Next to their role in endocytosis, several TPC subunits are also implicated in actin-regulated autophagosomal degradation. Inactivating TPC via the WDX mutation, however, does not impair autophagy, thus enabling specific and reversible modulation of endocytosis in planta.

Nationwide Evaluation of Quality of Care Indicators for Individuals with Severe Mental Illness and Diabetes Mellitus, Following Israel's Mental Health Reform.

Diabetes Mellitus (DM) is more common among individuals with severe mental illness (SMI). We aimed to assess quality-of-care-indicators in individuals with SMI following the 2015 Israel's Mental-Health-reform. We analyzed yearly changes in 2015-2019 of quality-of-care-measures and intermediate-DM-outcomes, with adjustment for gender, age-group, and socioeconomic status (SES) and compared individuals with SMI to the general adult population. Adults with SMI had higher prevalences of DM (odds ratio (OR) = 1.64; 95% confidence intervals (CI): 1.61-1.67) and obesity (OR = 2.11; 95% CI: 2.08-2.13), compared to the general population. DM prevalence, DM control, and obesity rates increased over the years in this population. In 2019, HbA1c testing was marginally lower (OR = 0.88; 95% CI: 0.83-0.94) and uncontrolled DM (HbA1c > 9%) slightly more common among patients with SMI (OR = 1.22; 95% CI: 1.14-1.30), control worsened by decreasing SES. After adjustment, uncontrolled DM (adj. OR = 1.02; 95% CI: 0.96-1.09) was not associated with SMI. Cardio-metabolic morbidity among patients with SMI may be related to high prevalences of obesity and DM rather than poor DM control. Effective screening for metabolic diseases in this population and social reforms are required.

Evolution of vascular plants through redeployment of ancient developmental regulators.

Vascular plants provide most of the biomass, food, and feed on earth, yet the molecular innovations that led to the evolution of their conductive tissues are unknown. Here, we reveal the evolutionary trajectory for the heterodimeric TMO5/LHW transcription factor complex, which is rate-limiting for vascular cell proliferation in Arabidopsis thaliana Both regulators have origins predating vascular tissue emergence, and even terrestrialization. We further show that TMO5 evolved its modern function, including dimerization with LHW, at the origin of land plants. A second innovation in LHW, coinciding with vascular plant emergence, conditioned obligate heterodimerization and generated the critical function in vascular development in Arabidopsis In summary, our results suggest that the division potential of vascular cells may have been an important factor contributing to the evolution of vascular plants.

Xylella fastidiosa's relationships: the bacterium, the host plants, and the plant microbiome.

Xylella fastidiosa is the causal agent of important crop diseases and is transmitted by xylem-sap-feeding insects. The bacterium colonizes xylem vessels and can persist with a commensal or pathogen lifestyle in more than 500 plant species. In the past decade, reports of X. fastidiosa across the globe have dramatically increased its known occurrence. This raises important questions: How does X. fastidiosa interact with the different host plants? How does the bacterium interact with the plant immune system? How does it influence the host's microbiome? We discuss recent strain genetic typing and plant transcriptome and microbiome analyses, which have advanced our understanding of factors that are important for X. fastidiosa plant infection.

Israeli COVID lockdowns mildly reduced overall use of preventive health services, but exacerbated some disparities.

BACKGROUND: During 2020, Israel experienced two COVID-19-related lockdowns that impacted the provision of primary and secondary preventive care. METHODS: We examined the month-by-month performance of selected preventive care services using data from Israel's national Quality Indicators in Community Healthcare program. Process of care measures included hemoglobin A1c (HbA1c) testing, cholesterol testing, colon cancer screening and mammography. Intermediate outcome measures included low-density lipoprotein control and HbA1c control. Measures were stratified by sex and by area-level socioeconomic position (SEP). Diabetes and mammography are presented in this abstract due to space limitations. RESULTS: Annual HbA1c testing among persons with diabetes decreased from 90.9% in 2019 to 88.0% in 2020. Performance of HbA1c tests during lockdown months was as low as half the usual amount. There were compensatory increases in testing during post-lockdown months that did not quite make up for the missed tests. In 2019, 9.0% of Israelis with diabetes had poor glycemic control (HbA1c ≥ 9.0); in 2020, it was 8.8%. In total, 4.5% fewer mammograms were performed in 2020 compared with 2019. Women in the lowest SEP level performed 10.4% fewer mammograms in 2020 than in 2019, while women in the highest SEP level performed 3.1% more mammograms. CONCLUSIONS: Prolonged COVID lockdowns in 2020 were associated with marked decreases in the performance of preventive health services during those months. Compensatory spikes following the end of lockdowns partly, but did not completely, make up for the missed care. COVID lockdowns may have exacerbated socioeconomic disparities in some preventive health services.

Is There a Familial Tendency for Same Sex Offspring? A Lesson Learned from a Large Non-Selected Israeli Population.

BACKGROUND: While the ratio of male to female births (sex-ratio at birth [SRB]) in humans is remarkably stable on the population level, there are many families with multiple same-sex offspring. OBJECTIVES: To identify a putative sub-population with skewed SRB and explore potential factors affecting the SRB. METHODS: A retrospective cohort study including 66,054 families with up to nine same-sex offspring evaluated between 2003 and 2015 at Hadassah-Hebrew University Medical Center. Outcome measures were observed prevalence and SRB of families with up to nine same-sex offspring in a single family. Analyses included the effect of parity, month and year of delivery, inter-delivery interval, and presence of a sequence of previous same-sex offspring on the SRB. RESULTS: The study comprised 193,411 live-born babies with SRB of 1.057 in favor of males. The proportion of SRB in families with up to nine same-sex offspring did not differ from the calculated presumed proportion. Furthermore, none of the tested factors (parity, month and year of delivery, inter-delivery interval, and the sequence of previous same-sex offspring) were significantly associated with SRB. CONCLUSIONS: SRB was not associated with any of the tested demographic characteristics. We could not identify a skew in SRB even in families with up to nine consecutive same sex offspring. This finding suggests that in the majority of the population the chance of a male or female fetus in each pregnancy remains similar in every pregnancy, regardless of any of the tested variables.

A comparison of methods for construction of fetal reference charts.

Reference charts for fetal measures are used for early detection of pregnancies that should be monitored closely. Construction of reference charts corresponds to estimation of quantiles of a distribution as a function of gestational age. Existing methods have been developed under various modeling assumptions, typically by fitting a polynomial regression to certain functionals of the distributions (e.g., mean, standard deviation, and quantiles). We use a large dataset to compare various existing methods for construction of reference charts. We also relax the assumptions of a parametric polynomial link between the distribution parameters and age and consider cubic splines and discretization of age in order to compare charts based on more flexible and simpler models, respectively. We compare the different methods using various tools and demonstrate the importance of considering performance measures calculated from age-stratified data. We also examine the question of sample size. We compare our charts to similar charts that have been recently published and emphasize that the source of an apparent heterogeneity should be investigated. We conclude that the choice of which method to use for construction of reference charts should take the following into account: available sample size, validity of normality assumption, and results of various performance measures.

Urinary organophosphate metabolite levels in Palestinian pregnant women: results of the Middle East Regional Cooperation Project.

The purpose of the study was to measure urinary organophosphate (OP) metabolites in Palestinian pregnant women, and to compare levels with those in pregnant women in Jerusalem and women from the general population in Israel. We measured six dialkyl phosphates in urine samples collected from 148 pregnant women from the West Bank area. Median total dimethyl phosphate (DM(total)) levels were significantly lower in Palestinian women compared to Jerusalem pregnant women and women in Israel (p = 0.041). In Palestinian women reporting that their place of residence was near an agricultural field, DM(total) levels were significantly higher (p = 0.037). Lower urinary excretion of dimethyl phosphate pesticide metabolites in Palestinian women compared to Israeli women may result from lower consumption of fruits and vegetables in the Palestinian population. Our findings highlight differences in OP pesticide exposure in populations with close geographical proximity but with differences in culture, diet, lifestyle, and regulatory oversight of pesticides.

A large head circumference is more strongly associated with unplanned cesarean or instrumental delivery and neonatal complications than high birthweight.

OBJECTIVE: Fetal size impacts on perinatal outcomes. We queried whether the fetal head, as the fetal part interfacing with the birth canal, might impact on obstetric outcomes more than birthweight (BW). We examined associations between neonatal head circumference (HC) and delivery mode and risk of perinatal complications as compared to high BW. STUDY DESIGN: This was an electronic medical records-based study of term singleton births (37-42 weeks' gestation) from January 2010 through December 2012 (N = 24,780, 6343 primiparae). We assessed risks of unplanned cesarean or instrumental delivery and maternal and fetal complications in cases with HC or BW ≥95th centile (large HC, high BW) vs those with parameters <95th centile (normal). Newborns were stratified into 4 subgroups: normal HC/normal BW (reference, n = 22,548, primiparae 5862); normal HC/high BW (n = 817, P = 213); large HC/normal BW (n = 878, P = 265); and large HC/high BW (n = 537, P = 103). Multinomial multivariable regression provided adjusted odds ratio (aOR) while controlling for potential confounders. RESULTS: Infants with HC ≥95th centile (n = 1415) were delivered vaginally in 62% of cases, unplanned cesarean delivery 16%, and instrumental delivery 11.2%; 78.4% of infants with HC <95th centile were delivered vaginally, 7.8% unplanned cesarean, and 6.7% instrumental delivery. Odds ratio (OR) for unplanned cesarean was 2.58 (95% confidence interval [CI], 2.22-3.01) and for instrumental delivery OR was 2.13 (95% CI, 1.78-2.54). In contrast, in those with BW ≥95th centile (n = 1354) 80.3% delivered vaginally, 10.2% by unplanned cesarean (OR, 1.2; 95% CI, 1.01-1.44), and 3.4% instrumental delivery (OR, 0.46; 95% CI, 0.34-0.62) compared to infants with BW <95th centile: spontaneous vaginal delivery, 77.3%, unplanned cesarean 8.2%, instrumental 7.1%. Multinomial regression with normal HC/normal BW as reference group showed large HC/normal BW infants were more likely to be delivered by unplanned cesarean (aOR, 3.08; 95% CI, 2.52-3.75) and instrumental delivery (aOR, 3.03; 95% CI, 2.46-3.75). Associations were strengthened in primiparae. Normal HC/high BW was not associated with unplanned cesarean (aOR, 1.18; 95% CI, 0.91-1.54), while large HC/high BW was (aOR, 1.93; 95% CI, 1.47-2.52). Analysis of unplanned cesarean indications showed large HC infants had more failure to progress (27.7% vs 14.1%, P < .001), while smaller HC infants had more fetal distress (23.4% vs 16.9%, P < .05). CONCLUSION: A large HC is more strongly associated with unplanned cesarean and instrumental delivery than high BW. Prospective studies are needed to test fetal HC as a predictive parameter for prelabor counseling of women with "big babies."

Pediatric overweight and obesity increased in Israel during the COVID-19 period.

Reports from many settings suggest that pediatric overweight and obesity increased in 2020 and 2021, presumably due to lifestyle changes associated with the COVID-19 pandemic. Many of these previous reports have relied on convenience samples or subsets of the population. Here, we present results of a longitudinal study of the entire population of Israel, a nation of approximately 9 million people, with the proportion with underweight, normal weight, overweight, and obesity at age 7 and at age 14-15, across the years 2017-2021. Our results show that the prevalence of overweight and obesity, which had been steady or improving through 2019, increased relatively quickly in 2020 and 2021. For example, among 7-year-olds, the percentage of children with obesity in 2019 was 6.8% (99% CI: 6.69-7.05), and by 2021, it had increased to 7.7% (99% CI: 7.53-7.93). There were important disparities in overweight and obesity based on SES; for example, the rate ratio for obesity comparing the poorest with the wealthiest 14-15-year-olds in 2019 was 1.63 (99% CI: 1.55-1.72). However, these disparities did not change meaningfully in 2020 and 2021, implying that while obesity did become more prevalent, this increase in prevalence was not differential across socioeconomic status. Like many other nations, Israel too experienced considerable increases in pediatric overweight and obesity in 2020-2021, erasing the improvements of the previous years among younger children.

Prenatal exposure to phthalates and emotional/behavioral development in young children.

INTRODUCTION: Endocrine disrupting chemicals (EDCs) such as phthalates, found in our daily environment, are nowadays suggested to be associated with adverse outcomes. Prenatal exposure was found associated with neurodevelopmental complications such as behavioral difficulties in school age children. AIM: To explore the association between intrauterine exposure to phthalates and emotional/behavioral development of 24 months old toddlers. METHODS: Women were recruited at 11-18 weeks of gestation and provided spot urine samples, analyzed for phthalate metabolites (DEHP, DiNP, MBzBP). Offspring were examined at 24 months of age, using standard maternal report, regarding developmental and behavioral problems (CBCL, ASQ-3, HOME questionnaires) (N = 158). To explore the associations between metabolite levels and developmental outcomes, multivariate GLM analysis (General Linear Model) was used according to tertiles and developmental scores on each developmental outcome. RESULTS: Associations of Di-(2-ethylhexyl) phthalate (DEHP) maternal exposure with behavioral-developmental outcomes were found only in boys. Compared with boys with lower DEHP maternal exposure, boys with high DEHP maternal exposure had lower developmental score in personal social abilities in the ASQ-3 questionnaire (50.68 + 8.06 and 44.14 + 11.02, high and low DEHP, respectively, p = 0.03), and more internalizing problems (for example, emotionally reactive score in high and low DEHP: 53.77 + 7.41 and 50.50 + 1.19, respectively, p = 0.029; anxious or depressed score: 53.38 + 5.01 and 50.75 + 1.34, respectively, p = 0.009; and somatic complaints scores 64.03 + 10.1 and 55.84 + 7.84, respectively, p = 0.003), and externalizing problems (49.28 + 8.59 and 43.33 + 9.11, respectively, p = 0.039). No differences were found in the development and behavior problems between high and low DEHP maternal exposure level in girls. CONCLUSION: Maternal DEHP metabolite concentrations measured in first trimester urine was associated with children's emotional/behavioral developmental problems in 24-months old boys, supporting accumulating evidence of DEHP as a potentially harming chemical and call for environmental attention.

Changing profile of health and function from age 70 to 85 years.

BACKGROUND: Old age has traditionally been considered to begin at age 65. The improving health and functional status observed among older people may necessitate reevaluation of this cut-off point. OBJECTIVE: To present the changing prevalence of common geriatric syndromes, functional parameters, common disease status and health care utilization, at ages 70, 78 and 85, in order to help address the question of when does contemporary aging actually begin. METHODS: Medical, psychosocial, cognitive, and functional status, and health service utilization at age 70, 78 and 85 were assessed through the Jerusalem Longitudinal Cohort Study (1990-2010), which prospectively followed a representative sample (born 1920-1921), of 1,861 people, all of whom underwent home-based comprehensive assessment. RESULTS: At age 70, the cohort had good health, low comorbidity, preserved cognition, mobility and independence in basic and instrumental activities of daily activities (ADL). Rising comorbidity, declining cognitive status, increasing depression, and difficulty in ADLs were seen at 78. By age 85, compared to age 70, comorbidity had tripled, depression, hearing and visual impairment, falls, dizziness and mobility problems had doubled; 23% of subjects had cognitive impairment, 42.5% suffered urinary incontinence, and dependence in basic and instrumental ADLs was common (37.8 and 51.7%, respectively). Home care was 4.5, 10.1, and 24.6%, and hospitalization in the previous year occurred among 12.3, 18.8 and 27.8% at ages 70, 78 and 85, respectively. CONCLUSIONS: At age 70, the overall health profile was favorable, prevalence of geriatric syndromes was low, cognitive and functional status was preserved, and health service utilization was low. The progressive deterioration seen at ages 78 and more profoundly so at age 85, suggest that a cut-off point beyond age 70 years may serve to better define entry into old age.

Infertility associated with precoital ovulation in observant Jewish couples; prevalence, treatment, efficacy and side effects.

BACKGROUND: Religious (halachic*) infertility' results from precoital ovulation prior to immersion in a ritual bath (mikveh) 7 days after menstruation, as mandated by Jewish religious law. Previous authors recommended treatment with estradiol to postpone ovulation and enhance pregnancy rates. OBJECTIVES: To evaluate the prevalence of halachic infertility in an ultra-Orthodox jewish community, and assess the efficacy of estradiol treatment in postponing ovulation and increasing pregnancy rates. METHODS: We reviewed 88 cycles, of which 23 were control cycles and 65 estradiol-treated cycles, and analyzed the files of 23 women who were treated with 6 mg estradiol/day from day 1 for 5 days of the cycle. RESULTS: The prevalence of precoital ovulation in the infertile population was 21%. Most of the patients (94%) ovulated before day 13 of the cycle. A short follicular phase due to low ovarian reserve orthyroid endocrinopathy was noted in 12% of the patients. While 64% of the women reported consultation with a Rabbinate authority, 68% of the patients sought medical therapy. Estradiol postponed ovulation for at least one day in 89% of the treatment cycles. Ovulation post-mikveh occurred in 73% of estradiol-treated cycles. The pregnancy rate was 12.5% per cycle and the cumulative pregnancy rate 35% per woman. Half the patients reported spotting during estradiol-treated cycles, and this postponed coitus. CONCLUSIONS: Precoital ovulation is a major reason for infertility among observant couples attending fertility clinics. Estradiol treatment is effective in delaying ovulation and restoring fecundity; however, it causes some adverse effects that may decrease its effectiveness.

Is the quality of donated semen deteriorating? Findings from a 15 year longitudinal analysis of weekly sperm samples.

BACKGROUND: Studies suggest that global semen quality is declining, but the debate remains open owing to geographic variation. OBJECTIVES: To evaluate temporal trends of sperm parameters - namely concentration, motility and total motile sperm count - in sperm donated during the period 1995-2009. METHODS: In a retrospective longitudinal cohort study we analyzed the sperm count and motility of 2182 semen samples provided on a weekly basis by 58 young, healthy, fertile, university-educated, paid donors. RESULTS: Despite the lowering of criteria for sperm parameters satisfactory for donation that were implemented in 2004, 38% of applicants for sperm donation are now rejected based on semen quality as compared to a third of applicants 10-15 years ago (P < 0.001). If the old strict criteria were in place 88% of candidates would be rejected today (P < 0.0001). Over the study period, the average sperm parameters dropped from a concentration of 106 +/- 25 million spermatozoa/ml with 79% +/- 4.3% motility to 68 +/- 14 million/ ml with 66% +/- 4.5% motile sperm (P < 0.0001, P < 0.0001, respectively). The total motile sperm count per ejaculate also decreased, from 66.4 +/- 18.2 million to 48.7 +/- 12 million (P < 0.005). When the previous criteria were implemented for the analysis of the latest group of sperm donors, only 18% of donors had an acceptable sperm quality, with an average concentration of 87 +/- 12 million spermatozoa/ml, 73% +/- 2.6% motile sperm and total motile sperm count of 53.1 +/- 3.8 million per ejaculate - still significantly lower than 15 years ago (P= 0.01, P= 0.003, P= 0.058 respectively). CONCLUSIONS: The rapid deterioration of sperm quality among fertile semen donors is alarming and may lead to cessation of sperm donation programs.

bHLH heterodimer complex variations regulate cell proliferation activity in the meristems of Arabidopsis thaliana.

Root, shoot, and lateral meristems are the main regions of cell proliferation in plants. It has been proposed that meristems might have evolved dedicated transcriptional networks to balance cell proliferation. Here, we show that basic helix-loop-helix (bHLH) transcription factor heterodimers formed by members of the TARGET OF MONOPTEROS5 (TMO5) and LONESOME HIGHWAY (LHW) subclades are general regulators of cell proliferation in all meristems. Yet, genetics and expression analyses suggest specific functions of these transcription factors in distinct meristems, possibly due to their expression domains determining heterodimer complex variations within meristems, and to a certain extent to the absence of some of them in a given meristem. Target gene specificity analysis for heterodimer complexes focusing on the LONELY GUY gene targets further suggests differences in transcriptional responses through heterodimer diversification that could allow a common bHLH heterodimer complex module to contribute to cell proliferation control in multiple meristems.

Molecular architecture of the endocytic TPLATE complex.

Eukaryotic cells rely on endocytosis to regulate their plasma membrane proteome and lipidome. Most eukaryotic groups, except fungi and animals, have retained the evolutionary ancient TSET complex as an endocytic regulator. Unlike other coatomer complexes, structural insight into TSET is lacking. Here, we reveal the molecular architecture of plant TSET [TPLATE complex (TPC)] using an integrative structural approach. We identify crucial roles for specific TSET subunits in complex assembly and membrane interaction. Our data therefore generate fresh insight into the differences between the hexameric TSET in Dictyostelium and the octameric TPC in plants. Structural elucidation of this ancient adaptor complex represents the missing piece in the coatomer puzzle and vastly advances our functional as well as evolutionary insight into the process of endocytosis.

High prevalence of left ventricular hypertrophy in octogenarian women: The Jerusalem Longitudinal Cohort Study.

BACKGROUND: Left ventricular hypertrophy (LVH) is more frequent in women and increases with age; however, it is unclear whether this finding is true in the very elderly. The objective of this study was to examine gender differences in the prevalence of LVH in a very elderly cohort. METHODS: Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Three hundred and thirty-nine of the subjects from the most recent set of data collection in 2005-2006 underwent echocardiography in addition to structured interviews and physical examination. RESULTS: The overall prevalence of LVH was high and significantly higher among women (60% vs 43%, p=0.0023). Systolic blood pressure (SBP) was significantly higher in women with LVH compared with women without LVH (p<0.01) and both groups of men (p<0.005). Women with LVH were three times more likely than women without LVH and 6.5 times more likely than men with LVH to believe that a BP of 160/100 mmHg represents their BP goal (p<0.05). CONCLUSIONS: This study demonstrates a high prevalence of LVH in a very elderly population, a finding significantly more pronounced in women and related to SBP.

Vascular transcription factors guide plant epidermal responses to limiting phosphate conditions.

Optimal plant growth is hampered by deficiency of the essential macronutrient phosphate in most soils. Plant roots can, however, increase their root hair density to efficiently forage the soil for this immobile nutrient. By generating and exploiting a high-resolution single-cell gene expression atlas of Arabidopsis roots, we show an enrichment of TARGET OF MONOPTEROS 5/LONESOME HIGHWAY (TMO5/LHW) target gene responses in root hair cells. The TMO5/LHW heterodimer triggers biosynthesis of mobile cytokinin in vascular cells and increases root hair density during low-phosphate conditions by modifying both the length and cell fate of epidermal cells. Moreover, root hair responses in phosphate-deprived conditions are TMO5- and cytokinin-dependent. Cytokinin signaling links root hair responses in the epidermis to perception of phosphate depletion in vascular cells.

Receptor kinase module targets PIN-dependent auxin transport during canalization.

Spontaneously arising channels that transport the phytohormone auxin provide positional cues for self-organizing aspects of plant development such as flexible vasculature regeneration or its patterning during leaf venation. The auxin canalization hypothesis proposes a feedback between auxin signaling and transport as the underlying mechanism, but molecular players await discovery. We identified part of the machinery that routes auxin transport. The auxin-regulated receptor CAMEL (Canalization-related Auxin-regulated Malectin-type RLK) together with CANAR (Canalization-related Receptor-like kinase) interact with and phosphorylate PIN auxin transporters. camel and canar mutants are impaired in PIN1 subcellular trafficking and auxin-mediated PIN polarization, which macroscopically manifests as defects in leaf venation and vasculature regeneration after wounding. The CAMEL-CANAR receptor complex is part of the auxin feedback that coordinates polarization of individual cells during auxin canalization.