Understanding the development of the auditory system is crucial for uncovering the molecular origins of hearing and its related disorders. During this development, spiral ganglion neurons extend peripheral fibers to cochlear hair cells and central projections to the cochlear nuclei, setting up a tonotopic map that connects the ear to the brainstem, enabling frequency-specific sound perception. This sensory information is then integrated bilaterally through a relay involving the superior olivary complex, lateral lemniscus, inferior colliculus, medial geniculate body, and the auditory cortex. While anatomical connectivity has been well-documented, recent advancements have revealed gene regulatory networks that coordinate the specification, differentiation, and connectivity of auditory neurons. In this review, we examine the molecular cascades guiding auditory system development, emphasizing transcriptional hierarchies and lineage determinants. Insights into these mechanisms enhance our understanding of auditory circuit formation and provide a critical foundation for therapeutic strategies aimed at addressing congenital and acquired hearing loss.

• Klíčová slova
• Auditory cortex, Brainstem, Cochlear hair cells, Cochlear nuclei, Genetic basis, Spiral ganglion neurons,
• Publikační typ
• časopisecké články MeSH

A gene cadre orchestrates the normal development of sensory and non-sensory cells in the inner ear, segregating the cochlea with a distinct tonotopic sound frequency map, similar brain projection, and five vestibular end-organs. However, the role of genes driving the ear development is largely unknown. Here, we show double deletion of the Iroquois homeobox 3 and 5 transcription factors (Irx3/5 DKO) leads to the fusion of the saccule and the cochlear base. The overlying otoconia and tectorial membranes are absent in the Irx3/5 DKO inner ear, and the primary auditory neurons project fibers to both the saccule and cochlear hair cells. The central neuronal projections from the cochlear apex-base contour are not fully segregated into a dorsal and ventral innervation in the Irx3/5 DKO cochlear nucleus, obliterating the characteristic tonotopic auditory map. Additionally, Irx3/5 deletion reveals a pronounced cochlear-apex-vestibular "vestibular-cochlear" nerve (VCN) bilateral connection that is less noticeable in wild-type control mice. Moreover, the incomplete segregation of apex and base projections that expands fibers to connect with vestibular nuclei. The results suggest the mammalian cochlear apex is a derived lagena reminiscent of sarcopterygians. Thus, Irx3 and 5 are potential evolutionary branch-point genes necessary for balance-sound segregation, which fused into a saccule-cochlea organization.

• Klíčová slova
• brainstem, cochlea, development, tectorial membrane,
• MeSH
• homeodoménové proteiny * genetika   metabolismus   MeSH
• kochlea * fyziologie   MeSH
• myši knockoutované * MeSH
• myši MeSH
• sakulus a utrikulus * fyziologie   MeSH
• sluchová dráha fyziologie   MeSH
• transkripční faktory * genetika   metabolismus   nedostatek   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• homeodoménové proteiny * MeSH
• Irx3 protein, mouse MeSH Prohlížeč
• Irx5 protein, mouse MeSH Prohlížeč
• transkripční faktory * MeSH

Transcription factors belonging to the basic helix-loop-helix (bHLH) family are key regulators of cell fate specification and differentiation during development. Their dysregulation is implicated not only in developmental abnormalities but also in various adult diseases and cancers. Recently, the abilities of bHLH factors have been exploited in reprogramming strategies for cell replacement therapy. One such factor is NEUROD1, which has been associated with the reprogramming of the epigenetic landscape and potentially possessing pioneer factor abilities, initiating neuronal developmental programs, and enforcing pancreatic endocrine differentiation. The review aims to consolidate current knowledge on NEUROD1's multifaceted roles and mechanistic pathways in human and mouse cell differentiation and reprogramming, exploring NEUROD1 roles in guiding the development and reprogramming of neuroendocrine cell lineages. The review focuses on NEUROD1's molecular mechanisms, its interactions with other transcription factors, its role as a pioneer factor in chromatin remodeling, and its potential in cell reprogramming. We also show a differential potential of NEUROD1 in differentiation of neurons and pancreatic endocrine cells, highlighting its therapeutic potential and the necessity for further research to fully understand and utilize its capabilities.

• Klíčová slova
• bHLH transcription factor, cell reprogramming, cell therapy, neurogenesis, pancreas,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH