146-65 million years ago


Heart and brain of an opossum:

opossum heartopossum brain

Therian mammals evolved changes in a number of systems which included additional areas of the cerebrum.

After monotremes, the spinal cord does not extend into sacral region. In the brains of therian mammals, the nuclei of the dorsal thalamus are more separated. Therian mammals possess cingulate and subcortical cortices, dorsal column nuclei, and parabrachial nuclei. The pretectum is more highly differentiated. The cerebellar hemispheres increased in size.
Therian mammals possess a presylvian sulcus of the cerebrum and share a secondary somatosensory area S2 and a central somatic sensory area. The cerebral cortex is composed of 6 layers of cells. Therians modified the dorsal cochlear nucleus to form an outer molecular layer, a layer of granule and fusiform cells, and a core of mixed cell types.
The external cuneate nucleus was separated from the cuneate-gracile nuclear complex. The lagena and ramulus lagenae have been lost. There was an increase in the size of the ventral cochlear connections in the medulla while dorsal connections decreased.
Theirans developed a distinct monolayer of mitral cells in olfactory bulb and optic tract fibers projecting to the anterior colliculus arrive at a deep layer rather than a superficial layer. The tympanic membrane was positioned vertically.

In therians, the spleen became more compact . Sequence comparisons indicate that MHC Class Ic genes diverged before the separation of therian mammals. The class II gene families are only known in therian mammals.

Although the embryonic external carotid artery is small and the stapedial artery is large, as in the condition in non-therian adult vertebrates, the external carotid grows into the branches of the stapedial artery which is subsequently reduced or absent. Therians developed umbilical arteries and the umbilical vein which empties into both the liver and the hepatic vein. The foramen ovale diverts most blood from lungs during fetal development.
The ancestral ß globin gene had duplicated to produce an proto-eta gene and a proto-beta gene prior to the separation of the lineages of therian mammals. Therians evolved an expression of globin after embryonic development and globin during embryonic development.

Marsupial lungs retain reptilian characteristics at birth ( a separate capillary in each air space, cuboidal epithelia lining alveoli) and are later modified in a mammalian fashion.