TMEM132A regulates mouse hindgut morphogenesis and caudal development.

Development

Department of Biology, Eberly College of Science and Huck Institute of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.

Published: July 2023

Caudal developmental defects, including caudal regression, caudal dysgenesis and sirenomelia, are devastating conditions affecting the skeletal, nervous, digestive, reproductive and excretory systems. Defects in mesodermal migration and blood supply to the caudal region have been identified as possible causes of caudal developmental defects, but neither satisfactorily explains the structural malformations in all three germ layers. Here, we describe caudal developmental defects in transmembrane protein 132a (Tmem132a) mutant mice, including skeletal, posterior neural tube closure, genitourinary tract and hindgut defects. We show that, in Tmem132a mutant embryos, visceral endoderm fails to be excluded from the medial region of early hindgut, leading directly to the loss or malformation of cloaca-derived genitourinary and gastrointestinal structures, and indirectly to the neural tube and kidney/ureter defects. We find that TMEM132A mediates intercellular interaction, and physically interacts with planar cell polarity (PCP) regulators CELSR1 and FZD6. Genetically, Tmem132a regulates neural tube closure synergistically with another PCP regulator Vangl2. In summary, we have identified Tmem132a as a new regulator of PCP, and hindgut malformation as the underlying cause of developmental defects in multiple caudal structures.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357036PMC
http://dx.doi.org/10.1242/dev.201630DOI Listing

Publication Analysis

Top Keywords

developmental defects
16
caudal developmental
12
neural tube
12
tmem132a regulates
8
caudal
8
tmem132a mutant
8
tube closure
8
defects
7
tmem132a
6
regulates mouse
4

Similar Publications

EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Am J Hum Genet

January 2025

Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany; Center for Rare Disease, University of Tübingen, 72076 Tübingen, Germany; Genomics for Health in Africa (GHA), Africa-Europe Cluster of Research Excellence (CoRE).

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

View Article and Find Full Text PDF

Toxicity of antimony in housefly after whole-life-cycle exposure: Changes in growth, development, redox homeostasis, mitochondrial function, and fecundity.

Ecotoxicol Environ Saf

January 2025

Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding 071002, China. Electronic address:

The increasing utilization of antimony (Sb) in manufacturing industries has led to the emergence of Sb contamination in the environment as a significant public health concern. To elucidate the toxicity of Sb and its mechanism of action, this study aimed to investigate the adverse effects of Sb on a cosmopolitan insect, housefly (Musca domestica), under a whole life cycle (from embryonic to adult stage) exposure through the examination of a suite of parameters, including biological, physiological, behavioral, and molecular endpoints. A range of Sb concentrations, including moderate contamination (0.

View Article and Find Full Text PDF

Point mutations in the ligand binding domain of retinoic acid receptor alpha (RARα) are linked to breast fibroepithelial tumor development, but their role in solid tumorigenesis is unclear. In this study, we assessed the functional effects of known RARα mutations on retinoic acid signaling using biochemical and cellular assays. All tested mutants exhibited reduced transcriptional activity compared to wild-type RARα and showed a dominant negative effect, a feature associated with developmental defects and tumor formation.

View Article and Find Full Text PDF

Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior. Mutations in Vangl are associated with developmental defects, including neural tube defects (NTDs), according to human cohort studies of sporadic and familial cases. The complex mechanisms underlying Vangl-mediated PCP signaling or Vangl-associated human congenital diseases have been hampered by the lack of molecular characterizations of Vangl.

View Article and Find Full Text PDF

Abnormalities in cerebellar subregions' volume and cerebellocerebral structural covariance in autism spectrum disorder.

Autism Res

January 2025

Department of Anatomy and Neurobiology, Research Center for Sectional and Imaging Anatomy, Shandong Provincial Key Laboratory of Mental Disorder, Shandong Key Laboratory of Digital Human and Clinical Anatomy, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

The cerebellum plays a crucial role in functions, including sensory-motor coordination, cognition, and emotional processing. Compared to the neocortex, the human cerebellum exhibits a protracted developmental trajectory. This delayed developmental timeline may lead to increased sensitivity of the cerebellum to external influences, potentially extending the vulnerability period for neurological disorders.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!