Biology subjects

Liu, F.-C.

Publications and source records attributed to Liu, F.-C..

3 recordsLinked to original sources

bioRxiv2022

Fgf9-Nolz-1-Wnt2 Signaling Axis Regulates Morphogenesis of the Lung

Morphological development of the lung requires complex signal crosstalk between the mesenchymal and epithelial progenitors. Elucidating the genetic cascades underlying the signal crosstalk is essential to understanding the morphogenesis of the lung. Here, we have identified Nolz-1/Znf503 as a mesenchymal lineage-specific transcriptional regulator that plays a key role in lung morphogenesis. The null mutation of Nolz-1 resulted in a severe hypoplasia phenotype, including decreased proliferation of mesenchymal cells, aberrant differentiation of epithelial cells, and defective growth of epithelial branches. The deletion of Nolz-1 also downregulated the expressions of Wnt2, Lef1, Fgf10, Gli3 and Bmp4. Mechanistically, we found that Nolz-1 regulated lung morphogenesis primarily through Wnt2 signaling. Loss of function and overexpression studies demonstrated that Nolz-1 transcriptionally activated Wnt2 and downstream {beta}-catenin signaling to control mesenchymal cell proliferation and epithelial branching. The Nolz-1-Wnt2 axis was also supported by evidence that exogenous Wnt2 could causally rescue defective proliferation and epithelial branching in Nolz-1 knockout lungs. Finally, we have identified Fgf9 as an upstream regulator of Nolz-1. Collectively, Fgf9-Nolz-1-Wnt2 signaling represents a novel signaling axis in the control of lung morphogenesis. These findings are also relevant to lung tumorigenesis in which a pathological function of Nolz-1 is involved.

developmental biology↗

bioRxiv2019

Developmental Characterization of Zswim5 Expression in the Progenitor Domains and Tangential Migration Pathways of Cortical Interneurons in the Mouse Forebrain

GABAergic interneurons play an essential role in modulating cortical networks. The progenitor domains of cortical interneurons are localized in developing ventral forebrain, including the medial ganglionic eminence (MGE), caudal ganglionic eminence (CGE), preoptic area (POA) and preoptic hypothalamic border domain (POH). Here, we characterized the expression pattern of Zswim5, an MGE-enriched gene in the mouse forebrain. At E11.5 to E13.5, prominent Zswim5 expression was detected in the subventricular zone (SVZ) of MGE, CGE, POA and POH of ventral telencephalon in which progenitors of cortical interneurons resided. At E15.5 and E17.5, Zswim5 remained detectable in the SVZ of pallidal primordium (MGE). Zswim5 mRNA was markedly decreased after birth and was absent in the adult forebrain. Interestingly, Zswim5 expression pattern resembled the tangential migration pathways of cortical interneurons. Zswim5-positive cells in the MGE appeared to migrate from the MGE through the SVZ of LGE to overlying neocortex. Indeed, Zswim5 was co-localized with Nkx2.1 and Lhx6, markers of progenitos and migratory cortical interneurons. Double labeling showed that Mash1/Ascl1-positive cells did not express Zswim5. Zswim5 expressing cells showed none or at most low levels of Ki67 but co-expressed Tuj1 in the SVZ of MGE. These results suggest that Zswim5 is immediately upregulated as progenitors exiting cell cycle to become postmitotic. Given that recent studies have elucidated that the cell fate of cortical interneurons is determined shortly after postmitotic, the timing of Zswim5 expression in early postmitotic cortical interneurons suggests a potential role of Zswim5 in regulation of neurogenesis and tangential migration of cortical interneurons.

neuroscience↗

bioRxiv2018

Repression of Dlx1/2 Signaling by Nolz-1/Znf503 is Essential for Parcellation of the Striatal Complex into Dorsal and Ventral Striatum

The division of the striatum into dorsal and ventral districts is of central clinical importance. The dorsal striatum is differentially affected in Huntingtons disease, dopamine in the ventral striatum is differentially spared in Parkinsons disease, and human brain imaging studies implicate the ventral striatum in addictive disorders. If fits that the dorsal striatum contains the cells of origin of the direct and indirect basal ganglia pathways for motor control. The ventral striatum is a node in neural circuits related to motivation and affect. Despite these striking neurobiologic contrasts, there is almost no information about how the dorsal and ventral divisions of the striatum are set up during development. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of developing striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and ventral striatum including the cell origin of the direct and indirect pathways. We show that Nolz-1 suppresses Dlx1/2 expression. Deletion of Nolz-1 or over-expression of Dlx1/2 can produce a striatal phenotype characterized by withered dorsal striatum and a swollen ventral striatum, and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. This evidence suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into the developing striatum.

neuroscience↗