Table 5: Examples of signaling pathways and disturbed neurodevelopmental processes involved in diverse neurodevelopmental pathologies.

Exposure to compounds which disrupt certain signaling pathways during brain development may impair key neurodevelopmental processes resulting in diverse neurodevelopmental pathologies. This table presents a few selected examples of signaling pathways dysfunction (CREB - cAMP Responsive Element Binding protein; TH- Thyroid Hormone; BDNF – Brain Derived Neurotrophic Factor, AKT - Protein Kinase B: PKB) based on in vivo studies cited in Chapter 6.1 How ready is the pathway concept for immediate use. (PSC - Pluripotent Stem Cells; NPC-Neural Precursor Cells, NCC - Neural Crest Cells; ESC: Embryonic Stem Cells.

Exemplary signaling pathways important for normal brain development	Neurodevelopmental pathologies associated with signalling pathway dysfunction	Disturbed neurodevelopmental processes
		Differentiation of PSC into NPC NPC proliferation	NCC proliferation and migration	Differentiation of ESCs towards neurons	Radial glia migration	Neurite outgrowth	Neuronal differentiation	Synapto-genesis	Neuronal network formation and function	Glial cells differentiation Myelination
CREB	Decreased activity: involved in deficit of cognitive function (AOP 13, 54, 42)		X Proliferation	X		X		X
TH	Decreased levels: deficit in cognitive function (AOP 54 &42)				X	X		X	X	X Oligoden-drocytes, myelination
BDNF	Decreased levels: impairment of learning and memory (AOP, 12,13, 54)					X		X	X
AKT	Pathway activation: brain overgrowth syndromes in humans	X NPC proliferation	X			X	X		X