Specification of catecholaminergic and serotonergic neurons

Abstract

The specification of neurotransmitter phenotype is an important aspect of neuronal fate determination. Substantial progress has been made in uncovering key extracellular signals and transcriptional regulators that control the mode of neurotransmission in several model systems, among which catecholaminergic and serotonergic neurons feature prominently. Here, we review our current knowledge of the regulatory circuits that direct neurotransmitter choice, and discuss the development of well-studied types of catecholaminergic and serotonergic neurons. One emerging concept is that different types of neuron use a similar core programme to control shared modes of neurotransmission, but recruit different factors that are specific for each neuronal type. Another is that most factors that specify neurotransmitter identity also control other features of the neuronal phenotype.

Neurogenin2 identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon

“…Following lethal exposure to CO 2 the embryos were removed and either taken for FACS analysis or immersion fixed overnight in 4% paraformaldehyde (PFA) in phosphate buffered saline (PBS; 0.1 M) at 8°C. Early stage (E10.5 -E13.5) or late stage (E15.5-17.5) fixed embryos were cryoprotected in 30% or 25% sucrose respectively and cryo-sectioned at a thickness of [12][13][14][15][16] µm.…”

“…Several developmental genes, such as Engrailed (En) 1 and 2, and Lmx1b, and cellular proteins such as aldehyde dehydrogenase-1 (Aldh1, also known as AHD-2), have been shown to be expressed in DA neuron precursors in the developing VM. However, the expression of these proteins is not restricted to the precursor pool, but is maintained also in the differentiated, post-mitotic mesDA neurons (9,14,21,30,32,37). Here we report that the proneural gene product Neurogenin2 (Ngn2) within the VM is expressed exclusively in the part of the proliferating ventricular zone (VZ), which gives rise to the migrating mesDA neuron precursors, but not in the differentiated, tyrosine hydroxylase (TH)-expressing postmitotic mesDA neurons.…”

Trim11 increases expression of dopamine β-hydroxylase gene by interacting with Phox2b

“…A regulatory network of extracellular signals and nuclear transcription factors has been demonstrated to be critical for specification of individual neurons [1][2][3][4]. Among the various phenotypes of a particular neuron, neurotransmitter identity is an important feature because it determines the nature of the chemical neurotransmission a given neuron will mediate, and influences the specific connectivity with target cells.…”

“…NA neurons are found in both the CNS and the PNS. The regulatory mechanism determining the NA neurotransmitter phenotype has been extensively studied, leading to the identification and functional characterization of critical signaling molecules and transcription factors [2,5]. Development of NA neurons in SG of the PNS and locus coeruleus (LC) of the CNS depends on bone morphogenetic proteins (BMPs) that are expressed in dorsal aorta and dorsal neural tube, respectively [2].…”

“…cAMP signaling pathway is also necessary for the induction of NA neurons in rat and avian NCSC culture. Both loss of function and gain of function studies showed that transcription factors, such as Mash1, Phox2b, Phox2a, dHand, and GATA-2/3, work cooperatively to specify NA neuron phenotype [2,[5][6][7][8].…”