Biology subjects

Goodrich, E. J.

Publications and source records attributed to Goodrich, E. J..

3 recordsLinked to original sources

bioRxiv2025

PROX1 Controls Cellular Patterning, Innervation and Differentiation in the Mouse Organ of Corti

The organ of Corti is divided into functional compartments responsible for hearing or cochlear amplification. A medial compartment containing inner hair cells innervated by Type I spiral ganglion neurons and a lateral compartment containing outer hair cells innervated by Type II spiral ganglion neurons. Supporting cells also differ, with lateral compartment pillar cells and Deiters cells developing specialized cellular structures to support outer hair cell electromotility. We bred organ of Corti-restricted Prox1 conditional knockout mice to study lateral compartment development because PROX1 is the first transcription factor expressed strictly in lateral compartment supporting cells. In the absence of Prox1, supporting cell numbers increased without corresponding changes in outer hair cells, and they appear incompletely differentiated based on morphological criteria. Outer hair cell number was not impacted but innervation was disrupted with many afferent neurons turning incorrectly towards the cochlear apex. RNAseq revealed no changes in gene expression that could account for the innervation phenotype. Therefore, we propose that PROX1 promotes pillar and Deiters cell differentiation and organization that has secondary effects on innervation but is not required for compartment specification.

developmental biology↗

bioRxiv2023

Emx2 Lineage Tracing Reveals Antecedent Patterns of Planar Polarity in the Mouse Inner Ear

The planar polarized organization of vestibular hair cells in the utricle and saccule is unique because these inner ear sensory organs contain two groups of hair cells with oppositely oriented stereociliary bundles that meet at a Line of Polarity Reversal (LPR). This organization allows the utricle or the saccule to detect motions directed in opposite directions, and is coordinated with patterns of neural innervation. EMX2 is a transcription factor that is only expressed by hair cells located on one side of the utricle or saccule where it reverses the orientation of their bundles and thereby establishes the position of the LPR. We generated Emx2-CreERt2 transgenic mice for genetic lineage tracing and demonstrate robust Emx2 expression at embryonic day 11.5 (E11.5), before hair cell specification, and when the nascent utricle and saccule have not yet segregated from a common prosensory domain. All hair cells derived from Emx2-CreERt2 lineage tracing at E11.5 are restricted to one side of the LPR in the mature utricle or saccule indicating that an antecedent LPR may be established by EMX2 at that stage. Consistent with this, Emx2-CreERt2 lineage tracing at E11.5 in Dreher mutant mice, where the utricle and saccule fail to segregate, labels a continuous field of cells distributed along one side of a fused utricular-saccular-cochlear organ. Altogether these observations reveal that the origin of the LPR is established in the developing prosensory domain, and that the presence or absence of Emx2 expression defines progenitor cells with distinct lineages that include hair cells with oppositely oriented stereociliary bundles.

developmental biology↗

bioRxiv2022

The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear

The vestibular maculae of the inner ear contain sensory receptor hair cells that detect linear acceleration, contribute to equilibrioception, and thereby coordinate posture and ambulatory movements. These hair cells are divided between two groups, separated by a line of polarity reversal (LPR), with oppositely oriented planar-polarized stereociliary bundles that detect motion in opposite directions. The transcription factor EMX2 is known to establish this planar polarized organization by regulating the distribution of the transmembrane receptor GPR156 at the hair cell surface in one group of cells, however those genes regulated by EMX2 in this context were previously not known. We have identified the serine threonine kinase STK32A as a downstream effector negatively regulated by EMX2. Stk32a is expressed in hair cells on one side of the LPR in a pattern complementary to Emx2 due to transcriptional repression. Stk32a is necessary to align the intrinsic polarity of the bundle with the core planar cell polarity (PCP) proteins in EMX2-negative regions, and is sufficient to reorient bundles when ectopically expressed in neighboring EMX2-positive regions. We demonstrate that STK32a reinforces LPR formation by regulating the apical localization of GPR156. These observations support a model in which bundle orientation is determined through separate mechanisms in hair cells on opposite sides of the LPR, with EMX2-mediated repression of Stk32a determining the position of the LPR. HighlightsO_LISTK32A is a planar polarity effector that is negatively regulated by the transcription factor EMX2 C_LIO_LIStk32a is necessary and sufficient to determine vestibular hair cell stereociliary bundle orientation C_LIO_LISTK32A contributes to the post-translational regulation of GPR156, preventing GPR156 localization in the absence of EMX2 C_LI

developmental biology↗