mab-21 was firstly identified in C. elegans as a pivotal gene for the sensory ray development in male tail. In mouse, there are two orthologs of mab-21, Mab21l1 and Mab21l2. Expression of Mab21l1 and Mab21l2 partially overlaps in the developing branchial arches, limb buds, midbrain and eyes. Among these two orthologs, Mab21l1 is expressed in the genital tubercle and lens, whereas Mab21l2 is expressed in the ventral body wall and umbilical cord. Mab21l2 was demonstrated to be essential for embryos survival.

To understand the functional domains of Mab21s in the development of mouse fore- and midbrain, systematic expression profiling of Mab21l1 and Mab21l2 in mid- and late embryonic stages was performed in this study. Evidence showed that the expressions of Mab21l1 and Mab21l2 la...[ Read more ]

mab-21 was firstly identified in C. elegans as a pivotal gene for the sensory ray development in male tail. In mouse, there are two orthologs of mab-21, Mab21l1 and Mab21l2. Expression of Mab21l1 and Mab21l2 partially overlaps in the developing branchial arches, limb buds, midbrain and eyes. Among these two orthologs, Mab21l1 is expressed in the genital tubercle and lens, whereas Mab21l2 is expressed in the ventral body wall and umbilical cord. Mab21l2 was demonstrated to be essential for embryos survival.

To understand the functional domains of Mab21s in the development of mouse fore- and midbrain, systematic expression profiling of Mab21l1 and Mab21l2 in mid- and late embryonic stages was performed in this study. Evidence showed that the expressions of Mab21l1 and Mab21l2 largely overlap in the developing thalamic eminence (TE), habenula, pretectum and dorsal midbrain. The expression domains of Mab21l1 and Mab21l2 in the fore- and midbrain implicate that these genes may be involved in the formation of those structure, or mediating a variety of biological processes, such as learning and memory, motor control, visual and auditory information integration. I further examine the potential role of Mab21l2 in brain by Cre-loxP system. Floxed Mab21l2 alleles were specifically removed in the neural progenitors by Nestin-cre. No morphological abnormality was found in the fore- and midbrain of the Mab21l2 conditional mutants. This result suggested that Mab21l2 is not required in the morphogenesis of both fore- and midbrain in mouse.

In addition to the understanding of Mab21l2 in eye development, we also generated Mab21l2^c.151C>T/+ (p.Arg51Cys/+) mouse model by CRISPR/Cas9 system to study the pathological phenotype of MAB21L2^c.151C>T/+ mutation, which was identified from eyeless human patients. The Mab21l2^c.151C>T/+ mutant mouse showed eyeless and malformation of limbs. The eye balls are missing, lens fail to develop, and remnants of the retina connecting to the hypothalamus are present. Expression level of Chx10 in the two hypothalamus-connecting abnormal structures is significantly reduced in developing Mab21l2^c.151C>T/+ mutant mice suggesting that Chx10 may act downstream of Mab21l2. Our study provides strong evidence for the pathogenicity of MAB21L2 mutations in human eye disease, suggesting pivotal role of MAB21L2 in morphogenesis of optic vesicle.