developmental genetics

schematic of fruit fly model of development

start with symmetric precusor cell, the microtubules and microfilaments form asymmetries (cytoskeleton) that lie in a particular direction, have TF and maternal supplied effects but also cytoskeleton is set up to allow them to form poles, forms amorphous blob to something that will be head,tail, back, and front to then segement units for very specific things

going from somatic cell to active protein

DNA transcription lead to primary transcript then splicing and other processes to mRNA to subcellular localization and post-transcriptional regulation to polypeptide to subunit complex formation to protein to protein modifications

Dros. development

segmentation at 10 hrs, organogenesis by 12 hr, larvae emerges 24 hr after fertilization forming 2 thoracic segments, head, and 8 abdominal segments 

fly stages 

diploid zygote nucleus then goes through 9 rounds of nuclear division to produce that multinucleate syncytium instead of cell dividing its nucleus and goes to form at posterior want to inject before that stage 

microtubules

polymer of multiple tubulin proteins so they have a direction

kinesin

motor proteins that carries vesicles (proteins, mRNA) using ATP-dependent motor action would move towards the positive pole (posterior)

dynein

protein that goes to the negative pole or anterior pole 

anterior-posterior axis formation

initially established by 2 TF in concentration gradients (BCD and HB-M) that are in the anterior end of developing embryo which turn on certain subset of genes at the anterior pole that are not going to be turned on in posterior pole because TF aren’t there

BCD-encoded by the bcd gene called bicoid

very steep gradient in early embryo because really high levels of proteins at anterior end and drops sharply down with none at the posterior end

HB-M encoded by HB gene called hunchback

slower but longer gradient and anterior gradient 

BCD gradient

BCD mRNA is packed during oogenesis (maternal factor), tethered to the negative end of microtubules so attached by dynein so high gradient at anterior and low posterior in mRNA terms

HB-M/NOS gradient

maternal origin but mRNA is uniformly distributed throughout oocyte and embryo (not tethered) but translation is blocked by NOS protein (nanos gene) whos mRNA is at the posterior end and move by kinesin and mRNA present anterior and less till not at all at posterior for HB-M

how are BCD and nanos tethered 

the 3’ UTR 

why do cells in the ventral produce spitz

gravity

how does ventral structures get made

when SPZ ligand binds to toll receptors intracellular signaling leads to activation of dorsal (TF)

what do the morphagens do (BCD, HB-M/NOS) do

turn on a subset of genes called gap genes so bicoid turns on anterior gap genes and nanos turns on posterior gap genes 

key not about genes turning on

certain promoters are sensitive to concentration of the TF so for bicoid some promoters are not going to be turned on as much because concentration went down

what does Gap gene expression do (hunchback and kruppel)

activate a set of genes called pair-rule genes important for segments expressed in repeating pattern of seven stripes (FTZ and eve)

pair rule genes 

within the anterior and posterior going to make segments that will affect the expression of segment polarity genes 

primary pair-rule genes

acted directly upon by the gap genes

secondary pair-rule genes

regulated by the primary pair-rule genes

segement polarity genes (segment number)

in stripes of 14 which set up polarity within an individual segment which set up anterior-posterior polarity within each segement

homeotic gene comples

targets by gap genes and exist in 2 clusters (ANT-C and BX-C) which specify which of the segments becomes thoracic and abdomen 

ANT-C

segment identity in the head an anterior throax

BX-C

identify posterior thorax and abdomen