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Biology subjects

Lew, H.

Publications and source records attributed to Lew, H..

2 recordsLinked to original sources

Emergence of Genetic Sex Determination in an Environmentally Sex-Determined Animal

The evolution of genetic sex determination (GSD) from environmental sex determination (ESD) remains a fundamental issue in evolutionary biology. However, the mechanisms driving such a transition, particularly in its earliest stages, are largely unknown. Here, we report on a genetic variant in the ESD species, Daphnia pulex, in which structural variations and selection on chromosome have suppressed recombination. This suppression has facilitated the accumulation of antagonistic features of the two chromosome- haplotypes, resulting in heterozygosity and differentiation of the sex-determining gene Dfh on two haplotypes. Consequently, this process has driven the emergence of a mixed-mating system, in which sex determination is jointly regulated by genetic and environmental factors. Additionally, we detected ongoing divergence in chromosomal structure between the two haplotypes at the population level. These findings suggest that processes analogous to early sex-chromosome evolution are occurring in this ESD species, offering novel insights into the molecular mechanisms underlying the emergence of GSD.

evolutionary biology↗

TMEM145 is a key component in stereociliary link structures of outer hair cells

Outer hair cells (OHCs) in the cochlea contain specialized stereociliary structures essential for auditory function. These include horizontal top connectors (HTCs), linking adjacent stereocilia and tectorial membrane-attachment crowns (TM-ACs), anchoring the tallest stereocilia to the tectorial membrane. The known molecular components of these structures, such as stereocilin, otogelin, otogelin-like, and tubby, lack transmembrane domains, suggesting the existence of anchoring proteins. This study identified TMEM145, a transmembrane protein with a Golgi dynamics (GOLD) domain, as a crucial OHC stereocilia component. TMEM145 was expressed in both OHCs and spiral ganglion neurons, with specific localization to TM-ACs and HTCs in OHCs. Tmem145 knockout (KO) mice exhibited profound hearing impairment at three weeks of age, with complete loss of distortion product otoacoustic emissions, indicating OHC dysfunction. Immunostaining and scanning electron microscopy revealed the absence of TM-ACs and HTCs in Tmem145 KO mice. In heterologous cell systems, TMEM145 interacted with stereocilin and tubby, facilitating their extracellular secretion. TMEM145 was undetectable in stereocilin KO and tubby mutant mice, indicating interdependence among these proteins. These findings establish TMEM145 as an essential membrane protein for the structural integrity of OHC stereocilia, providing insights into the molecular architecture of cochlear hair cells and their role in auditory function.

neuroscience↗