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Lin, J. M.

Publications and source records attributed to Lin, J. M..

2 recordsLinked to original sources

The transcription factor Tfap2e/AP-2ε plays a pivotal role in maintaining the identity of basal vomeronasal sensory neurons

The identity of individual neuronal cell types is defined by the expression of specific combinations of transcriptional regulators that control cell type-specific genetic programs. The epithelium of the vomeronasal organ of mice contains two major types of vomeronasal sensory neurons (VSNs): 1) the apical VSNs which express vomeronasal 1 receptors (V1r) and the G-protein subunit Gi2 and; 2) the basal VSNs which express vomeronasal 2 receptors (V2r) and the G-protein subunit Gao. Both cell types originate from a common pool of progenitors and eventually acquire apical or basal identity through largely unknown mechanisms.\n\nThe transcription factor AP-2{varepsilon}, encoded by the Tfap2e gene, plays a role in controlling the development of GABAergic interneurons in the main and accessory olfactory bulb (AOB), moreover AP-2{varepsilon} has been previously described to be expressed in the VSNs. Here we show that AP-2{varepsilon} is expressed in postmitotic VSNs after they commit to the basal differentiation program. Loss of AP-2{varepsilon} function resulted in reduced number of basal VSNs and in an increased number of neurons expressing markers of the apical lineage. Our work suggests that AP-2{varepsilon}, which is expressed in late phases of differentiation, is not needed to initiate the apical-basal differentiation dichotomy but for maintaining the basal VSNs identity by preventing the expression of apical genes. Moreover, our data suggest that differentiated VSNs of mice retain a notable level of plasticity.\n\nHighlightsO_LIThe VNO contains two major cell types that are segregated in apical and basal regions of the VNO\nC_LIO_LIAP-2{varepsilon} is expressed in postmitotic basal vomeronasal sensory neurons.\nC_LIO_LIAP-2{varepsilon} is essential to maintain the identity of basal vomeronasal sensory neurons.\nC_LI

developmental biology

Olfactory and vomeronasal innervation of the olfactory bulbs are not essential for GnRH-1 neuronal migration to the brain.

Gonadotropin releasing hormone-1 (GnRH-1) neurons migrate from the developing olfactory pit into the hypothalamus during embryonic development. Migration of the GnRH-1 neurons is required for mammalian reproduction as these cells control release of gonadotropins from the anterior pituitary gland. Disturbances in GnRH-1 cell migration, GnRH-1 synthesis, secretion or signaling lead to varying degrees of hypogonadotropic hypogonadism (HH), which impairs pubertal onset and fertility. HH associated with congenital olfactory defects is clinically defined as Kallmann Syndrome (KS).\n\nThe association of olfactory defects with HH in KS suggested potential direct relationship between defective olfactory axonal routing, lack of olfactory bulbs and aberrant GnRH-1 cell migration. However, it has never been experimentally proven that the formation of axonal connections of the olfactory and vomeronasal neurons to their functional targets are necessary for the migration GnRH-1 neurons to the hypothalamus. Loss-of-function of the Arx-1 homeobox gene leads to the lack of proper formation of the olfactory bulbs with abnormal axonal termination of olfactory sensory neurons (Yoshihara et al., 2005). We exploited the Arx-1null mouse line to investigate the role of the olfactory system (olfactory/vomeronasal fibers and OBs) in controlling GnRH-1 migration to the hypothalamus. Our data proves that correct development of the OBs, and axonal connection of the olfactory and vomeronasal sensory neurons to the forebrain are not needed for GnRH-1 neuronal migration. Moreover, we prove that the terminal nerve, which forms the GnRH-1 migratory scaffold, follows different guidance cues and differs in its genetic expression from olfactory and vomeronasal sensory neurons.\n\nSignificance StatementGonadotropin Releasing Hormone-1 (GnRH-1) neurons control the reproductive axis of vertebrates. During embryonic development, these neurons migrate from the olfactory pit to the hypothalamus. GnRH-1 cell migration is commonly believed to take place along the olfactory axons. Our work reveals that correct olfactory bulb development and targeting of the olfactory and vomeronasal sensory neurons to the brain are not required for this migration. Our work challenges the idea that GnRH-1 neuronal migration to the hypothalamus relies on correct routing of the olfactory and vomeronasal sensory neurons. We provide a new basis for interpreting genetic correlations between anosmia, lack of olfactory bulbs, and hypogonadotropic hypogonadism in Kallmann Syndrome.

neuroscience