Gene-environment interactions modulate the phenotypic severity in mouse models of congenital craniofacial syndromes.

Birth defects are the leading cause of infant mortality, and most inborn errors of development are multifactorial in origin, resulting from complex gene-environment interactions. Defining specific gene-environment interactions in the etiology and pathogenesis of congenital disorders is critically needed in the absence of genotype-phenotype correlation but is challenging. This is particularly true for congenital craniofacial anomalies, which account for approximately one-third of all birth defects, as they typically exhibit considerable inter-familial and intra-familial variability.

Genomic evolution of EGF-CFC genes in deuterostomes.

Background: EGF-CFC proteins are a bilaterian innovation, but they are best known for their roles in Nodal signaling during gastrulation and left-right patterning in vertebrates. Species with multiple family members show evidence of functional specialization. For example, in mouse, Cripto is required for gastrulation, whereas CFC1 is involved in left-right patterning.

Identification and characterization of short-chain dehydrogenase/reductase 3 (DHRS3) deficiency, a retinoic acid embryopathy of humans.

Purpose: Signaling by the morphogen all-trans retinoic acid (RA) is critical for embryonic development, during which its tissue concentration must be tightly regulated. We investigated 8 sibships (12 individuals) segregating 5 different homozygous variants of dehydrogenase/reductase 3 ), which encodes an embryonically expressed enzyme (short-chain dehydrogenase/reductase 3; also termed SDR16C1) that catalyzes the reduction of retinaldehyde to retinol, limiting excessive RA synthesis.

Methods: We assessed variant pathogenicity using comparative phenotypic and bioinformatic analysis, quantification of expression, and measurement of plasma retinoid metabolites.

An atypical basement membrane forms a midline barrier during left-right asymmetric gut development in the chicken embryo.

Correct intestinal morphogenesis depends on the early embryonic process of gut rotation, an evolutionarily conserved program in which a straight gut tube elongates and forms into its first loops. However, the gut tube requires guidance to loop in a reproducible manner. The dorsal mesentery (DM) connects the gut tube to the body and directs the lengthening gut into stereotypical loops via left-right (LR) asymmetric cellular and extracellular behavior.

Pre-oviposition development of the brown anole (Anolis sagrei).

Background: The brown anole, Anolis sagrei, has emerged as a representative squamate species for developmental studies during the past decades. Novel functional tools have been established to manipulate embryogenesis through genome editing or the introduction of small molecule inhibitors, and their effective use requires a thorough understanding of early anole embryogenesis. To enable precise and reproducible staging of anole embryos, we need knowledge of the progression of anole embryogenesis and morphogenesis.

The Society for Craniofacial Genetics and Developmental Biology 47th Annual Meeting.

The Society for Craniofacial Genetics and Developmental Biology (SCGDB) hosted its 47th Annual Meeting on September 9-10, 2024, at the Stowers Institute for Medical Research and Children's Mercy Research Institute in Kansas City, Missouri. On the opening day, Drs. Jean-Pierre Saint-Jeannet and Elizabeth Leslie received the SCGDB Distinguished Scientist Awards in recognition of their exceptional contributions to craniofacial biology.

Cell extrusion drives neural crest cell delamination.

Neural crest cells (NCC) comprise a heterogeneous population of cells with variable potency that contribute to nearly every tissue and organ throughout the body. Considered unique to vertebrates, NCC are transiently generated within the dorsolateral region of the neural plate or neural tube during neurulation. Their delamination and migration are crucial for embryo development as NCC differentiation is influenced by their final resting locations.

Rdh10-mediated Retinoic Acid Signaling Regulates the Neural Crest Cell Microenvironment During ENS Formation.

The enteric nervous system (ENS) is formed from vagal neural crest cells (NCC), which generate most of the neurons and glia that regulate gastrointestinal function. Defects in the migration or differentiation of NCC in the gut can result in gastrointestinal disorders such as Hirschsprung disease (HSCR). Although mutations in many genes have been associated with the etiology of HSCR, a significant proportion of affected individuals have an undetermined genetic diagnosis.

(veiled chameleon) chromosome-scale genome assembly and annotation provides insights into the evolution of reptiles and developmental mechanisms.

The family Chamaeleonidae comprises 228 species, boasting an extensive geographic spread and an array of evolutionary novelties and adaptations, but a paucity of genetic and molecular analyses. Veiled chameleon () has emerged as a tractable research organism for the study of squamate early development and evolution. Here we report a chromosomal-level assembly and annotation of the veiled chameleon genome.

Decrypting the phylogenetics history of EGF-CFC proteins Cripto and Cryptic.

EGF-CFC proteins are obligate coreceptors for Nodal signaling and are thus required for gastrulation and left-right patterning. Species with multiple family members show evidence of specialization. For example, mouse is required for gastrulation, whereas is involved in left-right patterning.

Identification and characterization of intermediate states in mammalian neural crest cell epithelial to mesenchymal transition and delamination.

Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it's unclear whether they exist during developmental EMT.

Dynamic changes in ocular shape during human development and its implications for retina fovea formation.

The human fovea is known for its distinctive pit-like appearance, which results from the displacement of retinal layers superficial to the photoreceptors cells. The photoreceptors are found at high density within the foveal region but not the surrounding retina. Efforts to elucidate the mechanisms responsible for these unique features have ruled out cell death as an explanation for pit formation and changes in cell proliferation as the cause of increased photoreceptor density.

Identification and characterization of intermediate states in mammalian neural crest cell epithelial to mesenchymal transition and delamination.

Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in both developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it's unclear whether they exist during developmental EMT.

An atypical basement membrane forms a midline barrier during left-right asymmetric gut development in the chicken embryo.

Correct intestinal morphogenesis depends on the early embryonic process of gut rotation, an evolutionarily conserved program in which a straight gut tube elongates and forms into its first loops. However, the gut tube requires guidance to loop in a reproducible manner. The dorsal mesentery (DM) connects the gut tube to the body and directs the lengthening gut into stereotypical loops via left-right (LR) asymmetric cellular and extracellular behavior.

rRNA transcription is integral to phase separation and maintenance of nucleolar structure.

Transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus is necessary for ribosome biogenesis, which is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis results in tissue specific disorders termed ribosomopathies in association with alterations in nucleolar structure. However, how rRNA transcription and ribosome biogenesis regulate nucleolar structure during normal development and in the pathogenesis of disease remains poorly understood.

Hypomyelination, hypodontia and craniofacial abnormalities in a Polr3b mouse model of leukodystrophy.

RNA polymerase III (Pol III)-related hypomyelinating leukodystrophy (POLR3-HLD), also known as 4H leukodystrophy, is a severe neurodegenerative disease characterized by the cardinal features of hypomyelination, hypodontia and hypogonadotropic hypogonadism. POLR3-HLD is caused by biallelic pathogenic variants in genes encoding Pol III subunits. While approximately half of all patients carry mutations in POLR3B encoding the RNA polymerase III subunit B, there is no in vivo model of leukodystrophy based on mutation of this Pol III subunit.