Biology subjects

Hopton, R. E.

Publications and source records attributed to Hopton, R. E..

3 recordsLinked to original sources

bioRxiv2023

The Role of Lrig1 in the Development of the Colonic Epithelium

Growth and specification of the mouse intestine occurs in utero and concludes after birth. While numerous studies have examined this developmental process in the small intestine, far less is known about the cellular and molecular cues required for colon development. In this study, we examine the morphological events leading to crypt formation, epithelial cell differentiation, areas of proliferation, and the emergence and expression of a stem and progenitor cell marker Lrig1. Through multicolor lineage tracing, we show Lrig1 expressing cells are present at birth and behave as stem cells to establish clonal crypts within three weeks after birth. In addition, we use an inducible knockout mouse to eliminate Lrig1 during colon development and show loss of Lrig1 restrains proliferation within a critical developmental time window, without impacting colonic epithelial cell differentiation. Our study illustrates the morphological changes that occur during crypt development and the importance of Lrig1 in the developing colon.

developmental biology↗

bioRxiv2018

Fibroblast growth factor receptors function redundantly during zebrafish embryonic development

Fibroblast growth factor (Fgf) signaling regulates many processes during development. In many cases, one tissue layer secretes an Fgf ligand that binds and activates an Fgf receptor (Fgfr) expressed by a neighboring tissue. Although many Fgf ligands have known requirements in development, less is known about the requirements for the receptors. We have generated null mutations in each of the five fgfr genes in zebrafish. Considering the many requirements for Fgf signaling throughout development and that null mutations in the mouse Fgfr1 and Fgfr2 genes are embryonic lethal, it was surprising that all zebrafish homozygous mutants are viable and fertile, with no discernable embryonic defect. Instead, we have discovered surprising complexity of the Fgf pathway, where multiple receptors are involved in coordinating developmental processes. For example, mutations in the ligand fgf8a cause loss of the midbrain-hindbrain boundary, whereas in the fgfr mutants, this phenotype is only seen in embryos that are triple mutant for fgfr1a;fgfr1b;fgfr2, but not in any single and double mutant combinations. We show that this apparent fgfr redundancy is also seen during the development of several other tissues, including posterior mesoderm, pectoral fins, viscerocranium, and neurocranium. These data therefore begin to define the Fgfrs that function with a particular Fgf ligand to regulate early development in zebrafish.\n\nSummary statementAnalysis of fibroblast growth factor receptor mutants in zebrafish shows that functional redundancy assures robustness of a core developmental signaling pathway.

developmental biology↗

bioRxiv2018

wnt4a Promotes Female Development and Reproductive Duct Elongation in Zebrafish

In laboratory strains of zebrafish, sex determination occurs in the absence of a typical sex chromosome and it is not known what regulates the proportion of animals that develop as male or female. Many sex determination and differentiation genes that act downstream of a sex chromosome are well conserved among vertebrates, but studies that test their contribution to this process have mostly been limited to mammalian models. In mammals, WNT4 is a signaling ligand that is essential for ovary and Mullerian duct development, where it function, in part, to antagonize the male-promoting FGF9 signal. Wnt4 is highly conserved in non-mammalian vertebrates, but it is not known if Wnt4 plays a role in sex determination and/or the differentiation of sex organs outside of mammals. This is an especially interesting question in teleost, such as zebrafish, because they lack an Fgf9 ortholog. Here we show that wnt4a is the ortholog of mammalian Wnt4, and that wnt4b was present in the last common ancestor of humans and zebrafish, but was lost in mammals. We found that wnt4a is expressed in the somatic cells of juvenile gonads during the time sex determination likely occurs. We show that wnt4a loss-of-function mutants develop predominantly as males and conclude that wnt4a activity promotes female sex determination in zebrafish. Additionally, both male and female wnt4a mutants are sterile because their reproductive ducts do not connect to the vent, where wnt4a is normally expressed. Yet when dissected from homozygous wnt4a mutant gonads, both sperm and eggs can produce fertile offspring. Together these results strongly argue that Wnt4a is a conserved regulator of female sex determination and reproductive duct development in non-mammalian vertebrates.\n\nSUMMARYWnt4 is a key regulator of ovary development in mammals, but it is not known if it plays a similar role in other vertebrates. Here we show that zebrafish wnt4a is the ortholog of mammalian Wnt4. We show that wnt4a is expressed in zebrafish somatic gonad cells during the time sex determination likely occurs. Through analysis of wnt4a mutants, we show that Wnt4a promotes female sex determination and the development of the male and female reproductive. We conclude that Wnt4/Wnt4a is likely a conserved regulator of ovarian and reproductive duct development in all vertebrates

developmental biology↗