Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo

Arlotta et al., 2005.

Ctip2 = Bcl11b
Otx1, TF in layers V and VI
Er81, TF in layer V, multiple neuronal subtypes
CsMNs = upper motor neurons
CPNs, CtPNs, and CsMNs were purified at four time points: early postmitotic (E18), more differentiated (P3, P6), and more mature and connected (P14).
FACS achieved >99% purity.
P14 CsMNs were so fragile that they were fixed in RNAlater following dissociation, and then were purified.
CsMN genes included transcription activators and repressors; zinc finger domain-containing proteins; cell surface proteins and receptors; calcium signaling molecules; genes involved in neuronal specification, cell adhesion, and axon guidance; and genes involved in critical signaling cascades.
In layer V, Lmo4 is found in CPNs but not in CsMNs, and Ctip2 is found in CsMNs but not in CPNs.
Ctip2 is expressed at high levels in CSMN and corticotectal neurons, but not callosal neurons. It is expressed at a much lower level in corticothalamic neurons and GABAergic neurons.

How are biological replicates different from hybridization replicates?
How does hiearchical clustering work?
What is the SAM method?
What is an EST?

EST = expressed sequence tag

This paper showed for the first time that there were genetically distinct neuronal subtypes within the same layer. They distinguished markers that were not merely layer-specific, but also subtype-specific.
They aimed to define the combinatorial program of novel genetic determinants of the CSMN population.

Reading a handful of key papers in depth

Now is the time for me to read some papers that are fundamental to my thesis work in painstaking detail. My learning from each paper will have its own series of posts.

A couple of reading strategies I plan to implement:
1. Take note of anything I don’t already know, then learn it
2. Ask experts to explain unclear statements
3. Point out the significance of each paper to the field at large

Major subtypes of projection neuron within the neocortex

Everything here comes directly from Molyneaux et al., 2007, sometimes verbatim.

Projection neurons in the neocortex come in several flavors:
I. Commissural/callosal, small to medium pyramidal size, extend an axon across the corpus callosum, never project out of the telencephalon.
      A. Single projection to the contra. cortex (layers II/III, V, VI)
      B. Dual projections to the contra. cortex and the ipsi. or contra. striatum (layer V)
      C. Dual projections to the contra. cortex and ipsi. frontal cortex (layer Va)
      D. Others
II. Corticofugal/subcortical
      A. Corticothalamic neurons (layer VI, minority in layer V)
      B. Subcerebral projection neurons (layer V)
            1. Corticotectal neurons, visual cortex, primary projections to superior colliculus, secondary projections to rostral pons
            2. Corticopontine neurons, primary projections to pons
            3. Corticospinal motor neurons, sensorimotor cortex, primary projections to spinal cord, secondary projections to striatum, red nucleus, caudal pons, and medulla.
            4. Others