I'm so excited to share my first preprint from @Lab_Pollen at @UCSF on the phylogenetic and spatial distribution of TAC3 interneurons. This story was an adventure filled with twists and turns we never saw coming. Check out the preprint and a summary below!.

RT @DanielMedinaC12: Beyond excited to share my main postdoctoral work. We developed a robust mouse cortical organoid system, which recapit….

(15/15) I had such a fun time working on this with our amazing collaborators @fennamk @debarardine @lab_paredes @aunoyp @Harwell_Lab @miguel_turrero and @mtvector and I hope you enjoy!.

(14/15) This leads us to conclude that evolution acts on a conserved repertoire of initial classes during neuronal development– teaching old cells new tricks – rather than inventing novel cell types.

(13/15) We find that Th interneurons in mouse and TAC3 interneurons in other mammals share a conserved initial class, which modifies its neuropeptide/neuromodulator expression as well as its destination throughout evolution.

(12/15) Finally, to resolve how these homologies may arise, we revisited mouse development by enriching for Nkx2.1+ newborn neurons and performed single cell RNA sequencing.

(11/15) Cross-species integrations and gene module comparisons of striatal INs from the ABC mouse atlas with published adult marmoset and human atlases suggested homology between Th INs in mouse and TAC3 INs in primates, consistent with similarities observed from @AMunozManchado.

(10/15) We examined adult striatal inhibitory neurons from the ABC mouse atlas @AllenInstitute and found a rare (~1.4% vs. 30% in primates) population of Tac2+ (ortholog of TAC3) inhibitory interneurons in a subset of mouse Th striatal interneurons – with a distinct ventral bias!.

(9/15) We began to wonder -- is this striatal cell type lost in mouse?.

(8/15) We surveyed published developing macaque data and performed additional RNAscope and did not observe these cells in the cortex of primates, suggesting this population is redistributed to the cortex in Laurasiatherian mammals (pigs and ferrets).

(7/15) Given the presence of these cells in the cortex of pigs and ferrets, we further examined the primate cortex for this initial class.

(6/15) Next, we revisited the ferret, this time in the context of development, and using both single cell RNA sequencing and RNAscope we found that the TAC3 interneuron initial class is also present in the striatum and cortex of ferrets.

(5/15) We next used RNAscope to examine the distribution of this initial class in the pig and found that not only are they in the striatum in pigs (like primates), but also have a novel population which migrates towards the cortex!.

(4/15) We uncovered that the initial class of TAC3 inhibitory interneurons, previously thought to be a primate-specific population, is indeed present in the developing pig!.

(3/15) We began by performing single cell RNA sequencing on the striatum and cortex of the developing pig (diverged ~94M years ago from human) to examine inhibitory interneuron initial class identities.

(2/15) These initial classes are largely conserved, with the notable exception of the initial class for the primate-specific striatal population of TAC3 interneurons. Or so we thought….

(1/15) Background: Telencephalic inhibitory interneurons are first specified in development as an initial class before maturing and taking on their final terminal identity.

My first first co-author paper on definitive endoderm and brain organoids in mouse EpiSCs is out in @Dev_journal from my time in the @TommyVierbuchen lab. A huge shoutout to my amazing co-author @DanielMedinaC12 I can’t wait to celebrate this together!

RT @bffswithbiology: Big presence from my grad program at #ISSCR2022. Couldnt even wrangle them all together for a pic. Best Developmental….

RT @DanielMedinaC12: v2.0 of our mouse brain organoid and definitive endoderm protocol is out! #organoids #brainorganoids.