Table 7.

Differentially regulated nervous system-specific genes detected in trisomy 18 and 21 AF supernatants

Differential regulationa	Gene	Gene name	Tissues expressing gene >30 MoMb	Gene function in nervous systemc
Downregulated in trisomy 18	PTPRD	Protein tyrosine phosphatase, receptor type, D	Fetal brain, prefrontal cortex, hypothalamus, amygdala, spinal cord	Implicated in axonal growth and guidance of motor neurons in mammals
	SOBP	Sine oculis binding protein homolog (Drosophila)	Fetal brain, amygdala, prefrontal cortex, whole brain	The protein encoded by this gene is a nuclear zinc finger protein that is involved in development of the cochlea. Defects in this gene linked to intellectual disability
	NEUROD2	Neurogenic differentiation 2	Cerebellum peduncles, fetal brain, cerebellum	Expression of this gene can induce transcription from neuron-specific promoters. The product of the human gene can induce neurogenic differentiation in non-neuronal cells in Xenopus embryos, and is thought to play a role in the determination and maintenance of neuronal cell fates
Upregulated in trisomy 18	PLEKHA4	Pleckstrin homology domain containing, family A (phosphoinositide binding-specific) member 4	Olfactory bulb	The second messenger phospatidylinositol 3-phosphate regulates a plethora of cellular processes
	PRPH2	Peripherin 2 (retinal degeneration, slow)	Pineal (day), pineal (night)	The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein found in the outer segment of both rod and cone photoreceptor cells. Defects in this gene are associated with both central and peripheral retinal degenerations
	GPM6A	Glycoprotein M6A	Amygdala, fetal brain, prefrontal cortex, occipital lobe, whole brain	An abundant cell surface protein on neurons in the central nervous system associated with differentiation and neuronal migration (Michibata et al. 2009). Downregulated in the brains of transgenic mice that overexpress tau, the neuronal phosphoprotein associated with Alzheimer’s disease (Woo et al. 2010)
Downregulated in trisomy 21	SOX11	SRY (sex determining region Y)-box 11	Fetal brain	A transcription factor involved in the regulation of embryonic development and in the determination of the cell fate; promotes neuronal maturation in the developing neural tube and is essential for establishment of pan-neuronal protein expression (Bergsland et al. 2006)
	DAAM2	Disheveled associated activator of morphogenesis 2	Spinal cord, hypothalamus, prefrontal cortex, retina, thalamus, caudate nucleus	Disheveled-binding protein transducing WNT signals to the PCP pathway. Involved in pivotal steps in neuronal cell differentiation and movement (Kida et al. 2004)
Upregulated in trisomy 21	MEF2C	Myocyte enhancer factor 2C	Fetal brain	Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. May also be involved in neurogenesis and in the development of cortical architecture
	CELSR2	Cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila)	Whole brain, prefrontal cortex, amygdala, medulla oblongata, cingulate cortex, parietal lobe	Receptor involved in cell/cell signaling during nervous system formation

^aAs identified from Slonim et al. 2009, Koide et al. 2011

^bBioGPS Gene Expression Atlas

^cEntrez gene or UniProt summaries unless references given