ORCID Profile
0000-0003-3372-6425
Current Organisation
University of South Australia
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Publisher: The Company of Biologists
Date: 2018
DOI: 10.1242/DEV.162552
Abstract: The adrenal medulla is composed of neuroendocrine chromaffin cells that secrete adrenaline into the systemic circulation to maintain physiological homeostasis and enable the autonomic stress response. How chromaffin cell precursors colonise the adrenal medulla, and how they become connected to central nervous system derived preganglionic sympathetic neurons remains largely unknown. By combining lineage tracing, gene expression studies, genetic ablation and the analysis of mouse mutants, we demonstrate that preganglionic axons direct chromaffin cell precursors into the adrenal primordia. We further show that preganglionic axons and chromaffin cell precursors require class 3 semaphorin (SEMA3) signalling through neuropilins (NRP) to target the adrenal medulla. Thus, SEMA3s serve as guidance cues to control formation of the adrenal neuroendocrine system by establishing appropriate connections between preganglionic neurons and adrenal chromaffin cells that regulate the autonomic stress response.
Publisher: Wiley
Date: 10-01-2015
DOI: 10.1111/DGD.12189
Abstract: Neural crest cells (NCCs) are highly migratory progenitor cells that give rise to a vast array of differentiated cell types. One of their key derivatives is the autonomic nervous system (ANS) that is comprised in part from chromaffin cells of the adrenal medulla and organ of Zuckerkandl, the sympathetic chain and additional prevertebral ganglia such as the celiac ganglia, suprarenal ganglia and mesenteric ganglia. In this review we discuss recent advances toward our understanding of how the NCC precursors of the ANS migrate to their target regions, how they are instructed to differentiate into the correct cell types, and the morphogenetic signals controlling their development. Many of these processes remain enigmatic to developmental biologists worldwide. Taking advantage of lineage tracing mouse models one of our own aims is to address the morphogenetic events underpinning the formation of the ANS and to identify the molecular mechanisms that help to segregate a mixed population of NCCs into pathways specific for the sympathetic ganglia, sensory ganglia or adrenal medulla.
Publisher: Springer Science and Business Media LLC
Date: 13-04-2017
DOI: 10.1186/S12861-017-0147-Z
Abstract: Cranial neural crest cells (NCCs) are a unique embryonic cell type which give rise to a erse array of derivatives extending from neurons and glia through to bone and cartilage. Depending on their point of origin along the antero-posterior axis cranial NCCs are rapidly sorted into distinct migratory streams that give rise to axial specific structures. These migratory streams mirror the underlying segmentation of the brain with NCCs exiting the diencephalon and midbrain following distinct paths compared to those exiting the hindbrain rhombomeres (r). The genetic landscape of cranial NCCs arising at different axial levels remains unknown. Here we have used RNA sequencing to uncover the transcriptional profiles of mouse cranial NCCs arising at different axial levels. Whole transcriptome analysis identified over 120 transcripts differentially expressed between NCCs arising anterior to r3 (referred to as r1-r2 migratory stream for simplicity) and the r4 migratory stream. Eight of the genes differentially expressed between these populations were validated by RT-PCR with 2 being further validated by in situ hybridisation. We also explored the expression of the Neuropilins ( Nrp1 and Nrp2 ) and their co-receptors and show that the A-type Plexins are differentially expressed in different cranial NCC streams. Our analyses identify a large number of genes differentially regulated between cranial NCCs arising at different axial levels. This data provides a comprehensive description of the genetic landscape driving ersity of distinct cranial NCC streams and provides novel insight into the regulatory networks controlling the formation of specific skeletal elements and the mechanisms promoting migration along different paths.
Publisher: EMBO
Date: 06-06-2018
Publisher: Springer Science and Business Media LLC
Date: 03-11-2014
Publisher: Life Science Alliance, LLC
Date: 03-08-2023
Abstract: Epithelial–mesenchymal transition is essential for tissue patterning and organization. It involves both regulation of cell motility and alterations in the composition and organization of the ECM—a complex environment of proteoglycans and fibrous proteins essential for tissue homeostasis, signaling in response to chemical and biomechanical stimuli, and is often dysregulated under conditions such as cancer, fibrosis, and chronic wounds. Here, we demonstrate that basonuclin-2 (BNC2), a mesenchymal-expressed gene, that is, strongly associated with cancer and developmental defects across genome-wide association studies, is a novel regulator of ECM composition and degradation. We find that at endogenous levels, BNC2 controls the expression of specific collagens, matrix metalloproteases, and other matrisomal components in breast cancer cells, and in fibroblasts that are primarily responsible for the production and processing of the ECM within the tumour microenvironment. In so doing, BNC2 modulates the motile and invasive properties of cancers, which likely explains the association of high BNC2 expression with increasing cancer grade and poor patient prognosis.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.BIOCEL.2013.02.014
Abstract: Neural crest cells are a transient population of stem cells that give rise to a erse range of cell types during embryonic development. Through gain-of-function and loss-of-function studies in several model organisms many key signalling pathways and cell-type specific transcription factors essential for neural crest cell development have been identified. However, the role of post-translational regulation remains largely unexplored. Here we review this cell type with a foray into the known and potential roles of the ubiquitination pathway in key signalling events during neural crest cell development.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.YDBIO.2013.09.024
Abstract: The integration of multiple morphogenic signalling pathways and transcription factor networks is essential to mediate neural crest (NC) cell induction, delamination, survival, stem-cell properties, fate choice and differentiation. Although the transcriptional control of NC development is well documented in mammals, the role of post-transcriptional modifications, and in particular ubiquitination, has not been explored. Here we report an essential role for the ubiquitin ligase Nedd4 in cranial NC cell development. Our analysis of Nedd4(-/-) embryos identified profound deficiency of cranial NC cells in the absence of structural defects in the neural tube. Nedd4 is expressed in migrating cranial NC cells and was found to positively regulate expression of the NC transcription factors Sox9, Sox10 and FoxD3. We found that in the absence of these factors, a subset of cranial NC cells undergo apoptosis. In accordance with a lack of cranial NC cells, Nedd4(-/-) embryos have deficiency of the trigeminal ganglia, NC derived bone and malformation of the craniofacial skeleton. Our analyses therefore uncover an essential role for Nedd4 in a subset of cranial NC cells and highlight E3 ubiquitin ligases as a likely point of convergence for multiple NC signalling pathways and transcription factor networks.
No related grants have been discovered for Rachael Lumb.