Table 1.

The reported downstream target genes of lines in Drosophila

Gene name	Gene symbol	Tissue/System	Up/Down	Human homologue	Putative roles in the development of the central nervous system in vertebrates	References
wingless	wg	Dorsal Epidermis	Up	WNT1	WNT1 protein involved in the proliferation and differentiation of neural progenitors. Wnt1 deficient mice embryos have showed severe abnormalities in the development of the midbrain and cerebellum.	[14,35,50]
rhomboid	rho (ve)	Dorsal Epidermis	Down	PARL	This gene encodes a mitochondrial integral membrane protein that plays an important regulatory role in mitochondrial-mediated apoptosis. Parl knockout mice undergo progressive multi-tissue atrophy, including atrophy in the thalamus and striatum, mediated by increased apoptosis.	[14,51,52]
orthopedia	otp	Hindgut	Up	OTP	This gene encodes a homeodomain-containing transcription factor that is implicated in the development of the brain, specifically hypothalamus, in vertebrates. Otp knockout mice displayed progressive impairment of crucial neuroendocrine developmental events.	[41,53-55]
decapentaplegic	dpp	Hindgut	Up	SMAD3	This protein functions as a transcriptional modulator thought to play a role in the in neural stem cells where it is essential to activate TGFβ-responsive genes activating the neural developmental program.	[41,56]
engrailed	en	Hindgut/Posterior spiracles	Up	EN1 and EN2	Both genes encode homeodomain-containing transcription factors that have been implicated in the control of mid-hindbrain pattern formation during embryogenesis. En1 deficient mice lack most of the cerebellum and midbrain, whereas En2 mutants survive with cerebellar defects.	[41,57,58]
retained	retn (dri)	Hindgut	Up	-		[41]
hedgehog	hh	Hindgut	Down	SHH	This gene encodes a protein that is crucial in patterning and cell-fate specification, particularly in the central nervous system. SHH plays different roles depending on its concentration, area, and timing of exposure.	[41,59]
outstretched	os (upd)	Hindgut	Down	-		[41]
Serrate	ser	Hindgut	Down	JAG2	The encoded protein is one of several ligands that activate Notch and related receptors. It was found in most neuron subtypes. Notch signaling plays a pivotal role in the regulation of vertebrate neurogenesis and brain development.	[41,60-62]
Brother of odd with entrails limited	bowl	Dorsal epidermis/foregut/hindgut/gonads/imaginal disc	Up	-		[40]
Cut	ct	Posterior spiracles	Up	-		[48]
Spalt major	salm	Posterior spiracles	Up	-		[48]
empty spiracles	ems	Posterior spiracles	Up	EMX2	The encoded protein is expressed in the dorsal telencephalon during development and is involved in regional patterning of the neocortex into defined functional areas. Emx2 deficient mice displayed defects in archipallium structures that are believed to play essential roles in learning, memory and behavior.	[48,63,64]
Stripe or Groovin	sr	Dorsal epidermis/muscle	Up	-		[44]
Cactus	cact	Testis	Down	NFKBIA	This gene encodes a member of the nuclear factor-κB (NF-κB) inhibitor family that is involved in inflammatory responses. NF-κB pathway plays a significant role in neurite outgrowth, activity-dependent plasticity, and cognitive function. NFKBIA is often deleted in glioblastomas.	[47,65,66]