Table 1 The reported downstream target genes of lines in Drosophila

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]