MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode

Mutations in human MAB21L1 cause aberrations in lens ectoderm morphogenesis and lead to congenital cerebellar, ocular, craniofacial, and genital (COFG) syndrome. Murine Mab21l1-null mutations cause severe cell-autonomous defects in lens formation leading to microphthalmia, and therefore is used as a mouse model for COFG syndrome. In this study, we investigated the early-onset, single-cell-level phenotypes of murine Mab21l1-null lens ectoderms using electron microscopy (EM) and single-cell RNA sequencing (scRNA-seq). EM and immunohistochemical analyses indicated endoplasmic reticulum stress in the 24- to 26-somite stage in Mab21l1-null lens placodes. scRNA-seq analysis revealed that 131 genes were downregulated and 148 were upregulated in Mab21l1-null lens ectoderms relative to the wild type. We successfully identified 21 lens-specific genes that were downregulated in Mab21l1-null cells including three key genes involved in lens formation: Pitx3, Maf, and Sfrp2. Moreover, gene ontology analysis of the 279 differentially expressed genes indicated enrichment in housekeeping genes associated with DNA/nucleotide metabolism prior to cell death. These findings suggest that MAB21L1 acts as a nuclear factor that modulates not only lens-specific gene expression but also DNA/nucleotide metabolic processes during lens placode formation.

Morphogenesis of the lens placode

For over 100 years, the vertebrate eye has been an important model system to understand cell induction, cell shape change, and morphogenesis during development. In the past, most of the studies examined histological changes to detect the presence of induction mechanisms, but the advancement of molecular biology techniques has made exploring the genetic mechanisms behind lens development possible. Despite the particular emphasis given to the induction of the lens placode, there are still many aspects of the cell biology of lens morphogenesis to be explored. Here, we will revisit the classical detailed description of early lens morphological changes, correlating it with the cell biology mechanisms and with the molecules and signaling pathways identified up to now in chick and mouse embryos. A detailed description of lens development stages helps better understand the timeline of the events involved in early lens morphogenesis. We then point to some key questions that are still open.

Mechanics of Optic Cup Invagination in the Embryonic Chick Eye

Invagination of epithelia is an essential morphogenetic process that occurs in early eye development. The mechanics of the tissue forces necessary for eye invagination are not yet understood [1]. The eyes begin as two optic vesicles that grow outwards from the forebrain and adhere to the surface ectoderm. At this point of contact, both the surface ectoderm and optic vesicle thicken, forming the lens placode and retinal placode, respectively. The two placodes then bend inward to create the lens vesicle and bilayered optic cup (OC) [1, 2].

Regulation of XFGF8 gene expression through SRY (sex-determining region Y)-box 2 in developing Xenopus embryos

Fibroblast growth factors (FGFs) function as mitogens and morphogens during vertebrate development. In the present study, to characterise the regulatory mechanism of FGF8 gene expression in developing Xenopus embryos the upstream region of the Xenopus FGF8 (XFGF8) gene was isolated. The upstream region of the XFGF8 gene contains two putative binding sites for the SRY (sex-determining region Y)-box 2 (SOX2) transcription factor. A reporter assay with serially deleted constructs revealed that the putative SOX2-binding motif may be a critical cis-element for XFGF8 gene activation in developing Xenopus embryos. Furthermore, Xenopus SOX2 (XSOX2) physically interacted with the SOX2-binding motif within the upstream region of the XFGF8 gene in vitro and in vivo. Depletion of endogenous XSOX2 resulted in loss of XFGF8 gene expression in midbrain–hindbrain junction, auditory placode, lens placode and forebrain in developing Xenopus embryos. Collectively, our results suggest that XSOX2 directly upregulates XFGF8 gene expression in the early embryonic development of Xenopus.